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  • 1.
    Almqvist, Ylva
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology, Radiology.
    Orlova, Anna
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology, Biomedical Radiation Sciences.
    Sjöström, Anna
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology, Biomedical Radiation Sciences.
    Jensen, Holger J.
    Danmark.
    Lundqvist, Hans
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology, Biomedical Radiation Sciences.
    Sundin, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology, Radiology.
    Tolmachev, Vladimir
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology, Biomedical Radiation Sciences.
    In vitro characterization of 211 At-labeled antibody A33: a potential therapeutic agent against metastatic colorectal carcinoma2005In: Cancer Biotherapy and Radiopharmaceuticals, ISSN 1084-9785, E-ISSN 1557-8852, Vol. 20, no 5, p. 514-523Article in journal (Refereed)
    Abstract [en]

    The humanized antibody A33 binds to the A33 antigen, expressed in 95% of primary and metastatic colorectal carcinomas. The restricted pattern of expression in normal tissue makes this antigen a possible target for radioimmunotherapy of colorectal micrometastases. In this study, the A33 antibody was labeled with the therapeutic nuclide 211At using N-succinimidyl para-(tri-methylstannyl)benzoate (SPMB). The in vitro characteristics of the 211At-benzoate-A33 conjugate (211At-A33) were investigated and found to be similar to those of 125I-benzoate-A33 (125I-A33) in different assays. Both conjugates bound with high affinity to SW1222 cells (Kd = 1.7 ± 0.2 nM, and 1.8 ± 0.1 nM for 211At-A33 and 125I-A33, respectively), and both showed good intracellular retention (70% of the radioactivity was still cell associated after 20 hours). The cytotoxic effect of 211At-A33 was also confirmed. After incubation with 211At-A33, SW1222 cells had a survival of approximately 0.3% when exposed to some 150 decays per cell (DPC). The cytotoxic effect was found to be dose-dependent, as cells exposed to only 56 DPC had a survival of approximately 5%. The 211At-A33 conjugate shows promise as a potential radioimmunotherapy agent for treatment of micrometastases originating from colorectal carcinoma.

  • 2.
    Almqvist, Ylva
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology, Radiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology, Biomedical Radiation Sciences.
    Steffen, Ann-Charlott
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology, Biomedical Radiation Sciences.
    Lundqvist, Hans
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology, Biomedical Radiation Sciences.
    Jensen, Holger
    Tolmachev, Vladimir
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Sundin, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology, Radiology.
    Biodistribution of At-211-Labeled humanized monoclonal antibody A332007In: Cancer Biotherapy and Radiopharmaceuticals, ISSN 1084-9785, E-ISSN 1557-8852, Vol. 22, no 4, p. 480-487Article in journal (Refereed)
    Abstract [en]

    Radioimmunotherapy (RIT) could be a possible adjuvant treatment method for patients with colorectal carcinoma. The A33 antigen is a promising RIT target, as it is highly and homogenously expressed in 95% of all colorectal carcinomas. In this study, the humanized monoclonal antibody A33 (huA33), targeting the A33 antigen, was labeled with the therapeutic nuclide 211At, and the biodistribution and in vivo targeting ability of the conjugate was investigated in an athymic mouse xenograft model. There was an accumulation of 211At in tumor tissue over time, but no substantial accumulation was seen in any organ apart from the skin and thyroid, indicating no major release of free 211At in vivo. At all time points, the uptake of 211At-huA33 was higher in tumor tissue than in most organs, and at 8 hours postinjection (p.i.), no organ had a higher uptake than tumor tissue. The tumor-to-blood ratio of 211At-huA33 increased with time, reaching 2.5 after 21 hours p.i. The highest absorbed dose was found in the blood, but the tumor received a higher dose than any organ other than the thyroid. An in vivo blocking experiment showed that 211At-huA33 binds specifically to human tumor xenografts in athymic mice. In conclusion, the favorable biodistribution and specific in vivo targeting ability of 211At-huA33 makes it a potential therapeutic agent for the RIT of metastatic colorectal carcinoma.

  • 3.
    Almqvist, Ylva
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology, Radiology.
    Steffen, Ann-Charlott
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology, Biomedical Radiation Sciences.
    Tolmachev, Vladimir
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology, Biomedical Radiation Sciences.
    Divgi, Chaitanya R.
    Sundin, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology, Radiology.
    In vitro and in vivo characterization of 177Lu‑huA33: A radioimmunoconjugate against colorectal cancer2006In: Nuclear Medicine and Biology, ISSN 0969-8051, E-ISSN 1872-9614, Vol. 33, no 8, p. 991-998Article in journal (Refereed)
    Abstract [en]

    INTRODUCTION: The humanized monoclonal antibody A33 (huA33) is a potential targeting agent against colorectal carcinoma since the A33 antigen is highly and homogenously expressed in >95% of all colorectal cancers, both primary tumors and metastases. The aim of this study was to determine the biodistribution and tumor-targeting ability of (177)Lu-labeled huA33. METHODS: huA33 was labeled with the beta-emitting therapeutic nuclide (177)Lu using the chelator CHX-A"-DTPA, and the properties of the (177)Lu-CHX-A"-huA33 ((177)Lu-huA33) conjugate was determined both in vitro and in vivo in a biodistribution study in nude mice xenografted with colorectal SW1222 tumor cells. RESULTS: The (177)Lu-huA33 conjugate bound specifically to colorectal cancer cells in vitro (with a K(D) value of 2.3+/-0.3 nM, determined by a saturation assay) and in vivo. The tumor uptake of (177)Lu-huA33 was very high, peaking at 134+/-21%ID/g 72 h postinjection (pi). Normal tissue uptake was low; radioactivity concentration in blood (which had the second highest radioactivity concentration) was lower than in tumor at all time points studied (8 h to 10 days). The tumor-to-blood ratio increased with time, reaching 70+/-30, 10 days pi. Throughout the study, the uptake of (177)Lu in bone (known to accumulate free (177)Lu) was low, and the fraction of protein-bound (177)Lu in plasma samples was high (95% to 99%). This indicates high stability of the (177)Lu-huA33 conjugate in vivo. CONCLUSION: The (177)Lu-huA33 conjugate shows a very favorable biodistribution, with an impressively high tumor uptake and high tumor-to-organ ratios, indicating that the conjugate may be suitable for radioimmunotherapy of colorectal cancer.

  • 4. Ambrosini, Valentina
    et al.
    Kunikowska, Jolanta
    Baudin, Eric
    Bodei, Lisa
    Bouvier, Catherine
    Capdevila, Jaume
    Cremonesi, Marta
    de Herder, Wouter W
    Dromain, Clarisse
    Falconi, Massimo
    Fani, Melpomeni
    Fanti, Stefano
    Hicks, Rodney J
    Kabasakal, Levent
    Kaltsas, Gregory
    Lewington, Val
    Minozzi, Silvia
    Cinquini, Michela
    Öberg, Kjell
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Endocrine Tumor Biology.
    Oyen, Wim J G
    O'Toole, Dermot
    Pavel, Marianne
    Ruszniewski, Philippe
    Scarpa, Aldo
    Strosberg, Jonathan
    Sundin, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Taïeb, David
    Virgolini, Irene
    Wild, Damian
    Herrmann, Ken
    Yao, James
    Consensus on molecular imaging and theranostics in neuroendocrine neoplasms2021In: European Journal of Cancer, ISSN 0959-8049, E-ISSN 1879-0852, Vol. 146, p. 56-73Article, review/survey (Refereed)
    Abstract [en]

    Nuclear medicine plays an increasingly important role in the management neuroendocrine neoplasms (NEN). Somatostatin analogue (SSA)-based positron emission tomography/computed tomography (PET/CT) and peptide receptor radionuclide therapy (PRRT) have been used in clinical trials and approved by the European Medicines Agency (EMA) and the US Food and Drug Administration (FDA). European Association of Nuclear Medicine (EANM) Focus 3 performed a multidisciplinary Delphi process to deliver a balanced perspective on molecular imaging and radionuclide therapy in well-differentiated neuroendocrine tumours (NETs). NETs form in cells that interact with the nervous system or in glands that produce hormones. These cells, called neuroendocrine cells, can be found throughout the body, but NETs are most often found in the abdomen, especially in the gastrointestinal tract. These tumours may also be found in the lungs, pancreas and adrenal glands. In addition to being rare, NETs are also complex and may be difficult to diagnose. Most NETs are non-functioning; however, a minority present with symptoms related to hypersecretion of bioactive compounds. NETs often do not cause symptoms early in the disease process. When diagnosed, substantial number of patients are already found to have metastatic disease. Several societies' guidelines address Neuroendocrine neoplasms (NENs) management; however, many issues are still debated, due to both the difficulty in acquiring strong clinical evidence in a rare and heterogeneous disease and the different availability of diagnostic and therapeutic options across countries. EANM Focus 3 reached consensus on employing 68gallium-labelled somatostatin analogue ([68Ga]Ga-DOTA-SSA)-based PET/CT with diagnostic CT or magnetic resonance imaging (MRI) for unknown primary NET detection, metastatic NET, NET staging/restaging, suspected extra-adrenal pheochromocytoma/paraganglioma and suspected paraganglioma. Consensus was reached on employing 18fluorine-fluoro-2-deoxyglucose ([18F]FDG) PET/CT in neuroendocrine carcinoma, G3 NET and in G1-2 NET with mismatched lesions (CT-positive/[68Ga]Ga-DOTA-SSA-negative). Peptide receptor radionuclide therapy (PRRT) was recommended for second line treatment for gastrointestinal NET with [68Ga]Ga-DOTA-SSA uptake in all lesions, in G1/G2 NET at disease progression, and in a subset of G3 NET provided all lesions are positive at [18F]FDG and [68Ga]Ga-DOTA-SSA. PRRT rechallenge may be used for in patients with stable disease for at least 1 year after therapy completion. An international consensus is not only a prelude to a more standardised management across countries but also serves as a guide for the direction to follow when designing new research studies.

  • 5.
    Andersson, Camilla
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Johansson, Birgitta
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Experimental and Clinical Oncology.
    Wassberg, Cecilia
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Johansson, Silvia
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Experimental and Clinical Oncology.
    Sundin, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Ahlström, Håkan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Assessment of Whether Patients' Knowledge, Satisfaction, and Experience Regarding Their 18F-Fluoride PET/CT Examination Affects Image Quality2016In: Journal of Nuclear Medicine Technology, ISSN 0091-4916, E-ISSN 1535-5675, Vol. 44, no 1, p. 21-25Article in journal (Refereed)
    Abstract [en]

    The aim of this study was to investigate patients’ previous knowledge, satisfaction and experience regarding a (18F)-fluoride positron emission tomography / computed tomography examination ((18F)-fluoride PET/CT) and to explore whether experienced discomfort during the examination or pain was associated with reduced image quality. A further aim was to explore whether patients’ health-related quality of life (HRQoL) was associated with their satisfaction and experiences of the examination.

    Methods: Fifty consecutive patients with a histopathological diagnosis of prostate cancer who were scheduled for (18F)-fluoride PET/CT were asked to participate in the study, which was performed between November 2011 and April 2013. A questionnaire was used to collect information regarding the patients’ previous knowledge and experience of the examination. Image quality assessment was performed according to an arbitrary scale. The EORTC-QLQ-C30 and QLQ-PR25 were used to assess HRQoL.

    Results: Forty-six patients (96%) completed the questionnaires. Twenty-six per cent of participants did not know at all what a (18F)-fluoride PET/CT examination was. The majority (52-70%) were to a very high degree satisfied with the care provided by the nursing staff but less satisfied with the information given prior to the examination. The image quality was similar in patients who were exhausted or claustrophobic during the examination and those who were not. No correlations between HRQoL and the participants’ experience of (18F)-fluoride PET/CT were found.

    Conclusion: The majority of participants were satisfied with the care provided by the nursing staff, but there is still room for improvement especially regarding the information prior to the examination. Long examination time may be strenuous, for the patient but there was no difference in image quality between patients who felt discomfort during the examination or pain and those who did not.

  • 6. Andersson, Jesper L
    et al.
    Sundin, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Section of Nuclear Medicine and PET.
    Valind, Sven
    A method for coregistration of PET and MR brain images1995In: Journal of Nuclear Medicine, ISSN 0161-5505, E-ISSN 1535-5667, Vol. 36, no 7, p. 1307-1315Article in journal (Refereed)
    Abstract [en]

    Combining MRI morphological data with functional PET data offers significant advantages in research as well as in many clinical situations. Automatic methods are needed, however, to coregister the data from the two modalities.

    METHODS:

    Simulated PET images were created by simple and automatic segmentation of MR images followed by the assignment of different uptake values to various tissue types. The simulated PET images were registered to actual PET images using a pixel-by-pixel, PET-PET registration method. The transformation matrix was then applied to the MR images. The method was used to register MRI data to PET transmission scans and emission scans obtained with FDG, nomifensine and raclopride. Validation was performed by comparing the results to those obtained by matching internal points manually defined in both volumes.

    RESULTS:

    Emission and transmission PET images were successfully registered to MR data. Comparison to the manual method indicated a registration accuracy on the order of 1-2 mm in each direction. No difference in accuracy between the different tracers was found. The error sensitivity for the method's assumptions seemed to be sufficiently low to allow complete automation of the method.

    CONCLUSION:

    We present a rapid, robust and fully automated method to register PET and MR brain images with sufficient accuracy for most clinical applications.

  • 7. Antoni, Gunnar
    et al.
    Omura, H
    Bergström, Mats
    Furuya, Y
    Moulder, R
    Roberto, A
    Sundin, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Section of Nuclear Medicine and PET.
    Watanabe, Y
    Långström, Bengt
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Medicinal Chemistry, Preclinical PET Platform.
    Synthesis of l-2,4-Diamino[4-11C]butyric acid and its use in some In vitro and In vivo tumour models1997In: Nuclear Medicine and Biology, ISSN 0969-8051, E-ISSN 1872-9614, Vol. 24, no 6, p. 595-601Article in journal (Refereed)
    Abstract [en]

    l-2,4-Diamino[4-11C]butyric acid (DAB) was synthesized by an enzyme catalysed carrier added (0.1 μmol KCN) reaction of hydrogen [11C]cyanide with O-acetyl-l-serine followed by reduction. l-[11C]DAB was obtained with a radiochemical purity higher than 96% and with a decay corrected radiochemical yield of 30–40% within a 32 min reaction time. The enantiomeric excess was 98%. The uptake of l-[11C]DAB was investigated in multicellular aggregates of six different cell lines and animal tumour models. l-[11C]DAB is potentially useful for the assessment of pharmacokinetics of l-DAB in vivo for part of its evaluation as an antitumoural agent, although its use for diagnostic purposes seems limited.

  • 8.
    Antonodimitrakis, Pantelis Clewemar
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Endocrine Tumor Biology.
    Olofsson, Helena
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Clinical and experimental pathology.
    Grimelius, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Experimental and Clinical Oncology.
    Sundin, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Wassberg, Cecilia
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Granberg, Dan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Endocrin Oncology.
    Skogseid, Britt
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Endocrine Tumor Biology.
    Eriksson, Barbro
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Endocrine Tumor Biology.
    Neuroendocrine tumors with syndromic vasoactive intestinal polypeptide hypersecretion: a retrospective study2017In: International Journal of Endocrine Oncology, Vol. 4, no 1, p. 9-22Article in journal (Refereed)
    Abstract [en]

    Aim: Vasoactive intestinal polypeptide producing neuroendocrine tumors are rare and cause severe hormonal symptoms. Patients/methods: Eighteen patients with vasoactive intestinal polypeptide producing neuroendocrine tumors were analyzed with reviews of medical records, radiology and tumor tissue specimens. Results: Twelve patients (67%) had liver metastases at diagnosis. Chemotherapy, somatostatin analogs and interferon were given as medical therapies. Streptozocin/5-fluorouracil produced an objective response in 40% of the evaluable patients. Somatostatin analogs gave a clinical/biochemical response in eight out of nine patients. Transarterial embolization of the liver and peptide receptor radionuclide therapy was given to refractory cases. Sixteen patients died during the observation period. The median overall survival from diagnosis was 102 months. Conclusion: Systemic chemotherapy and somatostatin analogs should be given in cases of advanced disease or for hormonal symptoms.

  • 9.
    Antonodimitrakis, Pantelis
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Endocrine Tumor Biology.
    Sundin, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Wassberg, Cecilia
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Granberg, Dan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Endocrin Oncology.
    Skogseid, Britt
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Endocrine Tumor Biology.
    Eriksson, Barbro
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Endocrine Tumor Biology.
    Streptozocin and 5-FU for the treatment of Pancreatic Neuroendocrine Tumors: Efficacy, Prognostic Factors and Toxicity2016In: Neuroendocrinology, ISSN 0028-3835, E-ISSN 1423-0194, Vol. 103, no 3-4, p. 345-353Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: In our center, the combination of streptozocin (STZ) and 5-fluorouracil (5-FU) has been used as the first-line treatment in the majority of patients with pancreatic neuroendocrine tumors (pNETs) over the past few decades. The objective of the current study was to assess the efficacy, prognostic factors and safety of the combination of STZ and 5-FU.

    PATIENTS AND METHODS: Medical records and radiological reports of 133 patients with pNETs who received the combination of STZ and 5-FU during the period 1981-2014 were retrospectively evaluated.

    RESULTS: Median survival from start of treatment was 51.9 months in the whole group. In the radiologically evaluable patients (n = 100) progression-free survival was 23 months. Complete response was reached in 3 patients (3%), partial response in 25 patients (25%), 64 patients (64%) had stable disease and 8 patients (8%) had progressive disease. In a multivariate analysis, surgery of the primary tumor and having a G3 tumor were significant positive and negative prognostic factors of survival from start of treatment, respectively. Having either a G3 tumor or stage IV tumor were significant prognostic factors for shorter progression-free survival. Chemotherapy had to be discontinued in 29 patients due to side-effects, of which kidney toxicity (mainly grade 1-2) was the most frequent.

    CONCLUSION: As shown in recent reports, the combination of STZ and 5-FU is effective in the treatment of pNETs in terms of survival and radiological response, and has an acceptable toxicity profile.

  • 10. Aziz, Q
    et al.
    Andersson, J L
    Valind, S
    Sundin, Anders
    Hamdy, S
    Jones, A K
    Foster, E R
    Långström, Bengt
    Thompson, D G
    Identification of human brain loci processing esophageal sensation using positron emission tomography1997In: Gastroenterology, ISSN 0016-5085, E-ISSN 1528-0012, Vol. 113, no 1, p. 50-59Article in journal (Refereed)
    Abstract [en]

    BACKGROUND & AIMS:

    Brain loci that process human esophageal sensation remain unidentified. The aim of this study was to identify the brain loci that process nonpainful and painful human esophageal sensation.

    METHODS:

    In 8 healthy subjects (7 men; age range, 24-47 years), distal esophageal stimulation was performed by repeatedly inflating a balloon at volumes that produced either no sensation, definite sensation, or pain. Two positron emission tomography scans were performed for each sensation using H2(15)O. Magnetic resonance brain scans were also performed in each subject, and the positron emission tomography data were coregistered with magnetic resonance scans. Analysis of covariance-corrected t images showing the contrasts definite sensation-baseline, pain-baseline, and pain-definite sensation were created.

    RESULTS:

    Nonpainful stimulation elicited bilateral activations along the central sulcus, insular cortex, and frontal/parietal operculum (P < 0.01). Painful stimulation produced more intense activations of the same areas and additional activation of the right anterior insular cortex and the anterior cingulate gyrus. Multiple areas of decreased activation were also observed; prominent among these was the right prefrontal cortex, which was inhibited during both nonpainful and painful stimulation.

    CONCLUSIONS:

    Esophageal sensation activates bilaterally the insula, primary somatosensory cortex, and operculum. The right anterior insular cortex and anterior cingulate gyrus process esophageal pain.

  • 11. Baudin, E.
    et al.
    Caplin, M.
    Garcia-Carbonero, R.
    Fazio, N.
    Ferolla, P.
    Filosso, P. L.
    Frilling, A.
    de Herder, W. W.
    Hörsch, D.
    Knigge, U.
    Korse, C. M.
    Lim, E.
    Lombard-Bohas, C.
    Pavel, M.
    Scoazec, J. Y.
    Sundin, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Berruti, A.
    Lung and thymic carcinoids: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up2021In: Annals of Oncology, ISSN 0923-7534, E-ISSN 1569-8041, Vol. 32, no 4, p. 439-451Article in journal (Refereed)
  • 12.
    Baudin, Eric
    et al.
    Inst Gustave Roussy, Oncol Endocrinienne & Med Nucl, Villejuif, France.
    Hayes, Aimee R.
    Royal Free Hosp, Neuroendocrine Tumour Unit, London, England.
    Scoazec, Jean-Yves
    Univ Lyon, Dept Pathol, Lyon, France.
    Filosso, Pier Luigi
    Univ Torino, Dept Thorac Surg, Turin, Italy.
    Lim, Eric
    Royal Brompton Hosp, Dept Thorac Surg, London, England.
    Kaltsas, Gregory
    Natl Univ Athens, Div Endocrinol, Dept Pathophysiol, Athens, Greece.
    Frilling, Andrea
    Imperial Coll London, Dept Surg & Canc, London, England.
    Chen, Jie
    Sun Yat Sen Univ, Affiliated Hosp 1, Dept Gastroenterol, Guangzhou, Guangdong, Peoples R China.
    Kos-Kudła, Beata
    Slaska Akad Med, Klin Endokrynol, Zabrze, Poland.
    Gorbunova, Vera
    Russian Acad Med Sci, FSBI NN Blokhin Russian Canc Res Ctr, Moscow, Russia.
    Wiedenmann, Bertram
    Charite Univ Med Berlin, Campus Charite Mitte, Dept Gastroenterol & Hepatol, Berlin, Germany; Charite Univ Med Berlin, Campus Virchow Klinikum, Berlin, Germany.
    Nieveen van Dijkum, Els
    Acad Med Ctr, Dept Surg, Amsterdam, Netherlands.
    Ćwikła, Jaroslaw B
    Univ Warmia & Mazury, Fac Med Sci, Dept Radiol, Olsztyn, Poland.
    Falkerby, Jenny
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Endocrin Oncology.
    Valle, Juan W.
    Univ Manchester, Inst Canc Sci, Christie NHS Fdn Trust, Dept Med Oncol, Manchester, Lancs, England.
    Kulke, Matthew H
    Harvard Med Sch, Dana Farber Canc Inst, Dept Med Oncol, Boston, MA USA.
    Caplin, Martyn E
    Royal Free Hosp, Neuroendocrine Tumour Unit, London, England.
    Sundin, Anders (Contributor)
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Tiensuu Janson, Eva (Contributor)
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Endocrin Oncology.
    Welin, Staffan (Contributor)
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Endocrin Oncology.
    Unmet Medical Needs in Pulmonary Neuroendocrine (Carcinoid) Neoplasms2019In: Neuroendocrinology, ISSN 0028-3835, E-ISSN 1423-0194, Vol. 108, no 1, p. 7-17Article in journal (Refereed)
    Abstract [en]

    Pulmonary carcinoids (PCs) display the common features of all well-differentiated neuroendocrine neoplasms (NEN) and are classified as low- and intermediate-grade malignant tumours (i.e., typical and atypical carcinoid, respectively). There is a paucity of randomised studies dedicated to advanced PCs and management principles are drawn from the larger gastroenteropancreatic NEN experience. There is growing evidence that NEN anatomic subgroups have different biology and different responses to treatment and, therefore, should be investigated as separate entities in clinical trials. In this review, we discuss the existing evidence and limitations of tumour classification, diagnostics and staging, prognostication, and treatment in the setting of PC, with focus on unmet medical needs and directions for the future.

  • 13.
    Berglund, Ake
    et al.
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology.
    Nygren, Peter
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology.
    Hagberg, Hans
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology.
    Pahlman, Lars
    Department of Surgical Sciences. Gastrointestinal Surgery.
    Sundin, Anders
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology.
    Sundström, Christer
    Department of Genetics and Pathology.
    [Limit investigation in cancer of unknown primary site]2005In: Lakartidningen, ISSN 0023-7205, Vol. 102, no 41, p. 2946-8, 2950Article in journal (Other scientific)
  • 14.
    Bergman, Antonina
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Magnusson, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Moore, Kevin
    Sundin, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Efficacy of the hepatocyte-specific contrast medium FP 736-04 for CT in two models of experimental diffuse liver disease1998In: Academic Radiology, ISSN 1076-6332, E-ISSN 1878-4046, Vol. 5, no Suppl 1, p. S13-S15; discussion S28-S30Article in journal (Refereed)
  • 15.
    Bergstrom, M
    et al.
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology.
    Juhlin, C
    Department of Surgical Sciences.
    Bonasera, TA
    Sundin, A
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology.
    Rastad, J
    Department of Surgical Sciences.
    Åkerström, Göran
    Department of Surgical Sciences.
    Langstrom, B
    Teknisk-naturvetenskapliga vetenskapsområdet, Chemistry, Department of Chemistry.
    PET imaging of adrenal cortical tumors with the 11beta-hydroxylase tracer11C-metomidate.2000In: J Nucl Med, Vol. 41, p. 275-Article in journal (Refereed)
  • 16. Bergström, Mats
    et al.
    Eriksson, Barbro
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Öberg, Kjell
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Sundin, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Ahlström, Håkan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Lindner, K J
    Bjurling, Pernilla
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology.
    Långström, Bengt
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Biochemistry and Organic Chemistry.
    In vivo demonstration of enzyme activity in endocrine pancreatic tumors: decarboxylation of carbon-11-DOPA to carbon-11-dopamine1996In: Journal of Nuclear Medicine, ISSN 0161-5505, E-ISSN 1535-5667, Vol. 37, no 1, p. 32-37Article in journal (Refereed)
    Abstract [en]

    METHODS:

    We used PET to characterize the uptake and decarboxylation of 11C-L-DOPA in vivo in two patients with endocrine pancreatic tumors: one glucagonoma and one gastrinoma.

    RESULTS:

    With L-DOPA labeled with 11C in the beta position, in which the radioactive label follows the molecule through decarboxylation to dopamine, significant uptake was observed in the tumors. With L-DOPA labeled in the carboxyl group, in which the label is rapidly eliminated from the tissue as 11CO2 if decarboxylation takes place, an almost complete lack of uptake is noted.

    CONCLUSION:

    This study shows that, using selective position labeling, an in vivo action of enzymatic activity can be observed with PET and that significant decarboxylation occurs in the tested endocrine pancreatic tumors. Also, marked retention of radioactivity occurs after treatment with somatostatin analogs. It is hypothesized that this is a reflection of a reduction of exocytosis which is induced by this treatment.

  • 17. Bergström, Mats
    et al.
    Juhlin, Claes
    Bonasera, Tomas A
    Sundin, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Section of Nuclear Medicine and PET.
    Rastad, Jonas
    Åkerström, Göran
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Endocrine Surgery.
    Långström, Bengt
    PET imaging of adrenal cortical tumors with the 11beta-hydroxylase tracer 11C-metomidate2000In: Journal of Nuclear Medicine, ISSN 0161-5505, E-ISSN 1535-5667, Vol. 41, no 2, p. 275-282Article in journal (Refereed)
    Abstract [en]

    The purpose of the study was to evaluate PET with the tracer 11C-metomidate as a method to identify adrenal cortical lesions.

    METHODS:

    PET with 11C-metomidate was performed in 15 patients with unilateral adrenal mass confirmed by CT. All patients subsequently underwent surgery, except 2 who underwent biopsy only. The lesions were histopathologically examined and diagnosed as adrenal cortical adenoma (n = 6; 3 nonfunctioning), adrenocortical carcinoma (n = 2), and nodular hyperplasia (n = 1). The remaining were noncortical lesions, including 1 pheochromocytoma, 1 myelolipoma, 2 adrenal cysts, and 2 metastases.

    RESULTS:

    All cortical lesions were easily identified because of exceedingly high uptake of 11C-metomidate, whereas the noncortical lesions showed very low uptake. High uptake was also seen in normal adrenal glands and in the stomach. The uptake was intermediate in the liver and low in other abdominal organs. Images obtained immediately after tracer injection displayed high uptake in the renal cortex and spleen. The tracer uptake in the cortical lesions increased throughout the examination. For quantitative evaluation of tracer binding in individual lesions, a model with the splenic radioactivity concentration assigned to represent nonspecific uptake was applied. Values derived with this method, however, did show the same specificity as the simpler standardized uptake value concept, with similar difference observed for cortical versus noncortical lesions.

    CONCLUSION:

    PET with 11C-metomidate has the potential to be an attractive method for the characterization of adrenal masses with the ability to discriminate lesions of adrenal cortical origin from noncortical lesions.

  • 18.
    Bergström, Mats
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences.
    Sörensen, Jens
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Section of Nuclear Medicine and PET.
    Khan, Tanweera Shaheena
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Juhlin, Claes
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences.
    Eriksson, Barbro
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Endocrine Tumor Biology.
    Sundin, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Section of Nuclear Medicine and PET.
    Bonasera, T.A.
    Fasth, K.-J.
    Långström, Bengt
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Section of Nuclear Medicine and PET.
    PET with [11C]-Metomidate for the Visualization of Adrenocortical Tumors and Discrimination from Other Lesions1999In: Clinical Positron Imaging, ISSN 1095-0397, E-ISSN 1878-5751, Vol. 2, no 6, p. 339-Article in journal (Refereed)
    Abstract [en]

    Purpose:

    The purpose of the study was to evaluate the potential role of PET with the adrenocortical-specific tracer 11C-metomidate in the characterization of incidentally found adrenal cortical lesions and in adrenocortical carcinomas.

    Methods:

    PET with 11C-metomidate was performed in 15 patients with unilateral adrenal mass confirmed by CT (incidentalomas) and in 9 additional patients with adrenocortical cancer. All incidentalomas subsequently underwent surgery, except 2 subjected to biopsy only. These lesions were histopathologically examined and diagnosed as adrenal cortical adenoma (n = 6; 3 nonfunctioning), adrenocortical carcinoma (n = 2) and nodular hyperplasia (n = 1). The remaining were non-cortical lesions including 1 pheochromocytoma, 1 myelolipoma, 2 adrenal cysts, and 2 metastases.

    Results:

    All lesions, except 1, with an adrenocortical origin were easily identified due to exceedingly high uptake of 11C-metomidate, whereas the non-cortical lesions showed very low uptake. The 1 false negative was a cancer that at surgery was found to be extensively necrotic. High uptake was also seen in normal adrenal glands. The tracer uptake kinetics indicated trapping of the tracer in the cortical lesions. For quantitative evaluation of tracer binding in individual lesions, the simple SUV concept was found to be equally accurate as more elaborate kinetic analyses.

    Conclusion:

    The patients presented and altogether over 40 PET investigations have demonstrated 11C-metomidate to be an attractive tracer for the characterization of adrenal masses with the ability to discriminate lesions of adrenal cortical origin from non-cortical lesions. Additionally the method allows the assessment of metastases from adrenocortical cancers, and the very high contrast has allowed partial whole-body examinations.

  • 19. Biermann, Martin
    et al.
    Johnsen, Boel
    Sørbye, Halfdan
    Følling, Magne
    Sundin, Anders
    Institutionen för Molekylär Medicin och Kirurgi, Karolinska Universitetssjukhuset, Stockholm.
    Bach-Gansmo, Tore
    [Positron emission tomography in neuroendocrine tumours]2009In: Tidsskrift for Den norske lægeforening, ISSN 0029-2001, E-ISSN 0807-7096, Vol. 129, no 15, p. 1474-1477Article in journal (Refereed)
    Abstract [no]

    BACKGROUND:

    Neuroendocrine tumours constitute a small group of malignancies; about 200 new patients are diagnosed in Norway annually. This article discusses problems associated with use of deoxyfluoroglucose (FDG) Positron Emission Tomography (PET) and other available options in patients with these conditions, as well as challenges related to introduction of new radiopharmaceutical agents.

    MATERIAL AND METHODS:

    The article is based on review of literature in connection with development of new guidelines for nuclear medicine examinations, supplemented with literature identified through a non-systematic search of Pubmed.

    RESULTS:

    A large proportion of these tumours grow slowly, and recent data show that 5-year survival is about 50 %. Neuroendocrine tumours are characterised by specific biochemical processes that enable tailoring of radiopharmaceutical agents for PET and consequently a more accurate diagnosis and improved follow-up of these patients.

    INTERPRETATION:

    As for other cancer types, diagnostics and detection of metastases are an important factor for correct treatment of neuroendocrine tumours. PET with FDG is of limited use for patients with this condition. New specific radiopharmaceutical agents for PET may imply detection of 90 % of all such tumours.

  • 20. Bodei, Lisa
    et al.
    Sundin, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Kidd, Mark
    Prasad, Vikas
    Modlin, Irvin M
    The Status of Neuroendocrine Tumor Imaging: From Darkness to Light?2015In: Neuroendocrinology, ISSN 0028-3835, E-ISSN 1423-0194, Vol. 101, no 1, p. 1-17Article in journal (Refereed)
    Abstract [en]

    Diagnostic imaging plays a pivotal role in the diagnosis, staging, treatment selection and follow-up for neuroendocrine tumors. The available diagnostic strategies are morphologic imaging, including computed tomography, magnetic resonance imaging (MRI) and ultrasound techniques, and molecular imaging, including scintigraphy with 111In-pentetreotide and positron emission tomography with 68Ga-DOTA-peptides, 18F-DOPA and 11C-5-HTP. A combination of anatomic and functional techniques is routinely performed to optimize sensitivity and specificity. The introduction of diffusion-weighted MRI and dynamic contrast-enhanced techniques represents a promising advance in radiologic imaging, whereas new receptor-binding peptides, including somatostatin agonists and antagonists, represent the recent most favorable innovation in molecular imaging. Future development includes the short-term validation of these techniques, but in extension also a more comprehensive multilevel integration of biologic information pertaining to a specific tumor and patient, possibly encompassing genomic considerations, currently evolving as a new entity denoted ‘precision medicine'. The ideal is a diagnostic sequence that captures the global status of an individual's tumor and encompasses a multidimensional characterization of tumor location, metabolic performance and target identification. To date, advances in imagery have focused on increasing resolution, discrimination and functional characterization. In the future, the fusion of imagery with the parallel analysis of biological and genomic information has the potential to considerably amplify diagnosis.

  • 21.
    Bozkurt, Murat Fani
    et al.
    Hacettepe Univ, Fac Med, Dept Nucl Med, Ankara, Turkey..
    Virgolini, Irene
    Med Univ Innsbruck, Dept Nucl Med, Innsbruck, Austria..
    Balogova, Sona
    Comenius Univ, Dept Nucl Med, Bratislava, Slovakia.;St Elisabeth Oncol Inst, Bratislava, Slovakia.;Tenon Hosp, AP HP, Dept Nucl Med, Paris, France.;Univ Paris 06, Paris, France..
    Beheshti, Mohsen
    St Vincents Hosp, PET CT Ctr, Dept Nucl Med & Endocrinol, Linz, Austria.;Paracelsus Med Univ, Dept Nucl Med, Salzburg, Austria..
    Rubello, Domenico
    Santa Maria della Misericordia Hosp, Dept Nucl Med, PET Ctr, Rovigo, Italy.;Santa Maria della Misericordia Hosp, Med Phys & Radiol, Rovigo, Italy..
    Decristoforo, Clemens
    Med Univ Innsbruck, Dept Nucl Med, Innsbruck, Austria..
    Ambrosini, Valentina
    Univ Bologna, Dept Expt Diagnost & Specialty Med DIMES, Bologna, Italy..
    Kjaer, Andreas
    Natl Univ Hosp, Dept Clin Physiol Nucl Med & PET, Rigshosp, Copenhagen, Denmark.;Univ Copenhagen, Copenhagen, Denmark..
    Delgado-Bolton, Roberto
    San Pedro Hosp, Dept Diagnost Imaging Radiol & Nucl Med, Logrono, Spain.;Ctr Biomed Res La Rioja CIBIR, Logrono, Spain..
    Kunikowska, Jolanta
    Med Univ Warsaw, Nucl Med, Warsaw, Poland..
    Oyen, Wim J. G.
    Inst Canc Res, London, England.;Royal Marsden NHS Fdn Trust, London, England..
    Chiti, Arturo
    Humanitas Univ, Dept Nucl Med, Rozzano, MI, Italy..
    Giammarile, Francesco
    Univ Lyon, Nucl Med, Lyon, France..
    Sundin, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Fanti, Stefano
    Univ Bologna, Dept Expt Diagnost & Specialty Med DIMES, Bologna, Italy..
    Guideline for PET/CT imaging of neuroendocrine neoplasms with Ga-68-DOTA-conjugated somatostatin receptor targeting peptides and F-18-DOPA2017In: European Journal of Nuclear Medicine and Molecular Imaging, ISSN 1619-7070, E-ISSN 1619-7089, Vol. 44, no 9, p. 1588-1601Article in journal (Refereed)
    Abstract [en]

    Purpose & Methods Neuroendocrine neoplasms are a heterogenous group of tumours, for which nuclear medicine plays an important role in the diagnostic work-up as well as in the targeted therapeutic options. This guideline is aimed to assist nuclear medicine physicians in recommending, performing, reporting and interpreting the results of somatostatin receptor (SSTR) PET/CT imaging using Ga-68-DOTA-conjugated peptides, as well as F-18-DOPA imaging for various neuroendocrine neoplasms. Results & Conclusion The previous procedural guideline by EANM regarding the use PET/CT tumour imaging with Ga-68-conjugated peptides has been revised and updated with the relevant and recent literature in the field with contribution of distinguished experts.

  • 22. Burman, Pia
    et al.
    Falhammar, Henrik
    Waldenström, Erik
    Sundin, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Bitzén, Ulrika
    11C-metomidate PET/CT detected multiple ectopic adrenal rest tumors in a woman with congenital adrenal hyperplasia2021In: Journal of Clinical Endocrinology and Metabolism, ISSN 0021-972X, E-ISSN 1945-7197, Vol. 106, no 2, p. e675-e679Article in journal (Refereed)
    Abstract [en]

    Context

    Women with congenital adrenal hyperplasia (CAH) may present with androgen excess that is difficult to control with conventional suppressive doses of glucocorticoids. Clinical management is challenging, and the woman is at great risk of developing steroid-induced complications.

    Patients and Methods

    A 32-year-old woman with salt-wasting CAH due to 21-hydroxylase deficiency underwent right-sided adrenalectomy because of a large myelolipoma. Over the years, androgens became increasingly difficult to suppress on prednisolone 5 + 0 + 2.5 mg daily, and at age 39 years the left adrenal with an enlarging myelolipoma was removed. A month later serum testosterone levels had increased from 4.1 preoperatively to 18.3 nmol/L (reference 0.2-1.8 nmol/L), and adrenocorticotropin levels from 32 to 283 pmol/L (reference < 14 pmol/L). No adrenal parenchyma was visualized on computed tomography (CT). In the further search for the source of the markedly elevated testosterone, positron emission tomography (PET) was performed with 2 different tracers, 18fluorodeoxyglucose (18FDG) reflecting glucose metabolism and 11C-metomidate, an inhibitor of 11-β-hydroxylase targeting adrenocortical tissue.

    Results

    18FDG-PET/CT with cosyntropin stimulation showed ovarian/paraovarian hypermetabolism, suggestive of adrenal rest tumors. Further characterization with 11C-metomidate PET/CT showed uptakes localized to the ovaries/adnexa, behind the spleen, and between the right crus diaphragmaticus and inferior vena cava.

    Conclusion

    Adrenal rest tumors can give rise to high androgen levels in spite of suppressive supraphysiological glucocorticoid doses. This case illustrates, for the first time, the value of 11C-metomidate PET as a sensitive method in documenting adrenal rest tumors, currently considered rare in women with CAH.

  • 23. Burman, Pia
    et al.
    Lethagen, ÅsaLinda
    Ivancev, Krasnodar
    Johansson, Leif
    Sundin, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology, Radiology.
    Dual bronchial carcinoids and Cushing's syndrome with a paradoxical response to dexamethasone and a false positive outcome of inferior petrosal sinus sampling2008In: European Journal of Endocrinology, ISSN 0804-4643, E-ISSN 1479-683X, Vol. 159, no 4, p. 483-8Article in journal (Refereed)
    Abstract [en]

    CONTEXT: Establishing the cause of Cushing's syndrome (CS) can be a considerable challenge, in particular in ectopic adrenocorticotropic hormone (ACTH) syndrome, and often requires a combination of biochemical tests and imaging procedures. SUBJECT: A 27-year-old man presented with signs of CS. P-ACTH levels were three times above the upper limit of normal (ULN) and free urinary cortisol around 2000 nmol/24 h. The work-up showed remarkable results. RESULTS: A 2-day low-dose dexamethasone suppression test demonstrated paradoxical increases in cortisol. Sampling from the bilateral inferior petrosal sinus sampling (BIPSS) showed a central to peripheral ACTH ratio of 4.7 after corticotrophin-releasing hormone (CRH) stimulation, i.e. indicated pituitary disease, but magnetic resonance imaging of the pituitary was normal. Computed tomography (CT) scan of the lungs showed two oval-shaped masses, 1.3 x 1.8 and 1.3 x 2 cm, in the middle lobe. Both were positive at somatostatin receptor scintigraphy, compatible with tumors or inflammatory lesions. Subsequently, (11)C-5-hydroxytryptophan-PET showed distinct uptake in the tumors but not elsewhere. Two carcinoids situated 3 cm apart, both staining for ACTH, were removed at surgery. CONCLUSION: This unique case with dual bronchial carcinoids inducing hypercortisolism illustrates the problems with identifying the source of ACTH in CS. Possibly, an abnormal regulation of ACTH production in response to dexamethasone, or steroid-induced tumor necrosis, explains the paradoxical outcome at dexamethasone suppression, and the false positive result at BIPSS reflects an unusual sensitivity of the pituitary corticotrophs to CRH in this patient. The work-up illustrates the great value of (11)C-5-hydroxytryptophan-PET as a diagnostic procedure when other investigations have produced ambiguous results.

  • 24. Byström, Per
    et al.
    Berglund, A.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology.
    Garske, Ulrike Garske
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Jacobsson, H.
    Sundin, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Nygren, Peter
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology.
    Frödin, J-E.
    Glimelius, Bengt
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology.
    Early prediction of response to first-line chemotherapy by sequential [18F]-2-fluoro-2-deoxy-D-glucose positron emission tomography in patients with advanced colorectal cancer2009In: Annals of Oncology, ISSN 0923-7534, E-ISSN 1569-8041, Vol. 20, no 6, p. 1057-1061Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: To evaluate [(18)F]-2-fluoro-2-deoxy-D-glucose (FDG) positron emission tomography (PET), for early evaluation of response to palliative chemotherapy and for prediction of long-term outcome, in patients with metastatic colorectal cancer (mCRC). PATIENTS AND METHODS: In a randomized trial, patients with mCRC received irinotecan-based combination chemotherapy. FDG-PET was carried out before treatment and after two cycles in 51 patients at two centers. Visual changes in tumor FDG uptake and changes measured semi-automatically, as standard uptake values (SUVs), were compared with radiological response after four and eight cycles. RESULTS: The mean baseline SUV for all tumor lesions per patient was higher in nonresponders than in responders (mean 7.4 versus 5.6, P = 0.02). There was a strong correlation between metabolic response (changes in SUV) and objective response (r = 0.57, P = 0.00001), with a sensitivity of 77% and a specificity of 76%. There was no significant correlation between metabolic response and time to progression (P = 0.5) or overall survival (P = 0.1). CONCLUSIONS: Although metabolic response assessed by FDG-PET reflects radiological tumor volume changes, the sensitivity and specificity are too low to support the routine use of PET in mCRC. Furthermore, PET failed to reflect long-term outcome and can, thus, not be used as surrogate end point for hard endpoint benefit.

  • 25. Calissendorff, Jan
    et al.
    Juhlin, Carl Christofer
    Sundin, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Bancos, Irina
    Falhammar, Henrik
    Adrenal myelolipomas2021In: The Lancet Diabetes and Endocrinology, ISSN 2213-8587, E-ISSN 2213-8595, Vol. 9, no 11, p. 767-776Article, review/survey (Refereed)
    Abstract [en]

    Adrenal myelolipomas are benign, lipomatous tumours with elements of myeloid cells, most of which present as adrenal incidentalomas and comprise 3·3-6·5% of all adrenal masses. Adrenal myelolipomas are usually unilateral (in 95% of cases), variable in size, most often found during midlife, and affect both sexes almost equally. On imaging, adrenal myelolipomas show pathognomonic imaging features consistent with the presence of macroscopic fat. Large adrenal myelolipomas can cause symptoms of mass effect, and can occasionally be complicated by haemorrhage. In the event of a concomitant adrenal cortical adenoma or hyperplasia, adrenal hormone excess might be detected in patients with adrenal myelolipoma. Patients with congenital adrenal hyperplasia exhibit a higher prevalence of adrenal myelolipomas than other patient groups, and are at risk of developing large and bilateral lesions. This Review discusses the pathogenesis, clinical presentation, and management of adrenal myelolipomas.

  • 26. Calissendorff, Jan
    et al.
    Maret, Eva
    Sundin, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science.
    Falhammar, Henrik
    Ileal neuroendocrine tumors and heart: not only valvular consequences2015In: Endocrine, ISSN 1355-008X, E-ISSN 1559-0100, Vol. 48, no 3, p. 743-755Article, review/survey (Refereed)
    Abstract [en]

    Ileal neuroendocrine tumors (NETs) often progress slowly, but because of their generally nonspecific symptoms, they have often metastasized to local lymph nodes and to the liver by the time the patient presents. Biochemically, most of these patients have increased levels of whole blood serotonin, urinary 5-hydroxyindoleacetic acid, and chromogranin A. Imaging work-up generally comprises computed tomography or magnetic resonance imaging and somatostatin receptor scintigraphy, or in recent years positron emission tomography with Ga-68-labeled somatostatin analogs, allowing for detection of even sub-cm lesions. Carcinoid heart disease with affected leaflets, mainly to the right side of the heart, is a well-known complication and patients routinely undergo echocardiography to diagnose and monitor this. Multitasking surgery is currently recognized as first-line treatment for ileal NETs with metastases and carcinoid heart disease. Open heart surgery and valve replacement are advocated in patients with valvular disease and progressive heart failure. When valvulopathy in the tricuspid valve results in right-sided heart failure, a sequential approach, performing valve replacement first before intra-abdominal tumor-reductive procedures are conducted, reduces the risk of bleeding. Metastases to the myocardium from ileal NETs are seen in <1-4.3% of patients, depending partly on the imaging technique used, and are generally discovered in those affected with widespread disease. Systemic treatment with somatostatin analogs, and sometimes alpha interferon, is first-line medical therapy in metastatic disease to relieve hormonal symptoms and stabilize the tumor. This treatment is also indicated when heart metastases are detected, with the addition of diuretics and fluid restriction in cases of heart failure. Myocardial metastases are rarely treated by surgical resection.

  • 27. Calissendorff, Jan
    et al.
    Sundin, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology. Department of Radiology, Karolinska University Hospital, Stockholm, Sweden .
    Falhammar, Henrik
    68Ga-DOTA-TOC-PET/CT detects heart metastases from ileal neuroendocrine tumors2014In: Endocrine, ISSN 1559-0100, Vol. 47, no 1, p. 169-176Article in journal (Refereed)
    Abstract [en]

    Metastases from ileal neuroendocrine tumors (NETs) to the myocardium are rare and generally seen in patients with widespread metastatic NET disease. The objectives of this investigation were to describe the frequency of intracardiac metastases in ileal NET patients examined by 68Ga-DOTA-TOC-PET/CT and to describe the cases in detail. All 68Ga-DOTA-TOC-PET/CT examinations performed at the Karolinska University Hospital since 2010 until April 2012 were reviewed. In all, 128 out of 337 examinations were in patients with ileal NETs. Four patients had seven myocardiac metastases, yielding a frequency of 4.3 % in patients with ileal NETs. One patient had cardiac surgery while three were treated with somatostatin analogs. The cardiac metastases did not affect the patients’ activity of daily life. 68Ga-DOTA-TOC-PET/CT is an established imaging modality in identifying cardiac metastases in ileal NETs. Prospective studies are needed to confirm the true clinical value of 68Ga-DOTA-TOC-PET/CT in detecting cardiac metastases in both ileal and non-ileal NETs.

  • 28.
    Capdevila, Jaume
    et al.
    Vall Hebron Univ Hosp, VHIO, Barcelona, Spain.
    Bodei, Lisa
    Mem Sloan Kettering Canc Ctr, New York, NY USA.
    Davies, Philippa
    Royal Free Hosp, Neuroendocrine Tumour Unit, London, England.
    Gorbounova, Vera
    Inst Russian Acad Med Sci, Dept Oncol, Moscow, Russia.
    Jensen, Robert T.
    NIH, Bethesda, MD USA.
    Knigge, Ulrich P.
    Univ Copenhagen, Dept Surg, Copenhagen, Denmark.
    Krejs, Guenter J.
    Med Univ Graz, Graz, Austria.
    Krenning, Eric
    Erasmus MC, Cyclotron Rotterdam BV, Rotterdam, Netherlands.
    O'Connor, Juan Manuel
    Alexander Fleming Inst, Caba, Argentina.
    Peeters, Marc
    Antwerp Univ Hosp, Dept Oncol, Antwerp, Belgium.
    Rindi, Guido
    Univ Cattolica Sacro Cuore, Fdn Policlin Univ A Gemelli IRCCS Roma, Rome, Italy.
    Salazar, Ramon
    Catalan Inst Oncol, Oncobell Program, IDIBELL, Cerca,Ciberonc, Barcelona, Spain.
    Vullierme, Marie-Pierre
    Beaujon Hop Assistance Publ, Radiol Dept, Paris, France.
    Pavel, Marianne E.
    Friedrich Alexander Univ Erlangen Nurnberg, Univ Klinikum Erlangen, Erlangen, Germany.
    Sundin, Anders (Contributor)
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Tiensuu Janson, Eva (Contributor)
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Endocrin Oncology.
    Welin, Staffan (Contributor)
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Endocrin Oncology.
    Unmet Medical Needs in Metastatic Lung and Digestive Neuroendocrine Neoplasms2019In: Neuroendocrinology, ISSN 0028-3835, E-ISSN 1423-0194, Vol. 108, no 1, p. 18-25Article in journal (Refereed)
    Abstract [en]

    Unmet medical needs are not infrequent in oncology, and these needs are usually of higher magnitude in rare cancers. The field of neuroendocrine neoplasms (NENs) has evolved rapidly during the last decade, and, currently, a new WHO classification is being implemented and several treatment options are available in the metastatic setting after the results of prospective phase III clinical trials. However, several questions are still unanswered, and decisions in our daily clinical practice should be made with limited evidence. In the 2016 meeting of the advisory board of the European Neuroendocrine Tumor Society (ENETS), the main unmet medical needs in the metastatic NENs setting were deeply discussed, and several proposals to try to solve them are presented in this article, including biomarkers, imaging, and therapy.

  • 29. Caplin, Martyn
    et al.
    Sundin, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Nillson, Ola
    Baum, Richard P
    Klose, Klaus J
    Kelestimur, Fahrettin
    Plöckinger, Ursula
    Papotti, Mauro
    Salazar, Ramon
    Pascher, Andreas
    ENETS Consensus Guidelines for the management of patients with digestive neuroendocrine neoplasms: colorectal neuroendocrine neoplasms2012In: Neuroendocrinology, ISSN 0028-3835, E-ISSN 1423-0194, Vol. 95, no 2, p. 88-97Article in journal (Refereed)
  • 30.
    Carlsson, Jörgen
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology, Biomedical Radiation Sciences.
    Blomquist, Erik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology, Oncology.
    Gedda, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology, Biomedical Radiation Sciences.
    Liljegren, Åsa
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology, Biomedical Radiation Sciences.
    Malmström, Per-Uno
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Urology.
    Sjöström, Anna
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology, Biomedical Radiation Sciences.
    Sundin, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology, Radiology.
    Westlin, Jan-Erik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology, Oncology.
    Zhao, Qinghai
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology, Biomedical Radiation Sciences.
    Tolmachev, Vladimir
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology, Biomedical Radiation Sciences.
    Lundqvist, Hans
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology, Biomedical Radiation Sciences.
    Conjugate chemistry and cellular processing of EGF-dextran1999In: Acta Oncologica, ISSN 0284-186X, E-ISSN 1651-226X, Vol. 38, no 3, p. 313-321Article in journal (Refereed)
    Abstract [en]

    Conjugates with specific binding to the epidermal growth factor receptor, EGFR, of interest for radionuclide based imaging and therapy were prepared using mouse epidermal growth factor, mEGF, and dextran. In one type of conjugate, mEGF was coupled to dextran by reductive amination in which the free amino group on the mEGF N-terminal reacted with the aldehyde group on the reductive end of dextran. The end-end coupled conjugate could be further activated by the cyanopyridinium agent CDAP, thereby introducing tyrosines to the dextran part. In the other type of conjugate, the cyanylating procedure using CDAP was applied, first to activate dextran and then allowing for the amino terminus of mEGF to randomly attach to the dextran. In the latter case, radionuclide-labelled tyrosines or glycines could be added in the same conjugation step. All types of mEGF-dextran conjugates had EGFR-specific binding since the binding could be displaced by an excess of non-radioactive mEGF. The conjugates were to a large extent internalized in the test cells and the associated radioactivity was retained intracellularly for different times depending on both the type of cells and conjugate applied. Different intracellular 'traffic routes' for the radionuclides are discussed as well as applications for both imaging and therapy.

  • 31. Castano, J. P.
    et al.
    Sundin, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Maecke, H. R.
    Villabona, C.
    Vazquez-Albertino, R.
    Navarro, E.
    Öberg, Kjell
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Endocrine Oncology.
    Gastrointestinal neuroendocrine tumors (NETs): new diagnostic and therapeutic challenges2014In: Cancer Metastasis Review, ISSN 0167-7659, E-ISSN 1573-7233, Vol. 33, no 1, p. 353-359Article, review/survey (Refereed)
    Abstract [en]

    This paper summarizes the current understanding of the biology of somatostatin receptor (sst), role of immunotherapy in neuroendocrine tumor (NET), new agents for PPRT, and methods to assess response and clinical benefit in NET. One of the most interesting aspects of sst biology is the recent discovery of truncated variants of the sst5 receptor subtype with unique tissue distribution and response to somatostatin (SST). These truncated receptors are associated with bad patient prognosis, decreased response to SST analogs, and may be new targets for diagnoses and treatment. IFN remains a cost-effective agent, particularly in classic mid gut carcinoids, and there is interest to continue examining immunotherapy's in this disease. PRRT remains a key strategy for treatment and imaging. In addition to the classic agents, there are a series of new agents targeting other receptors such as the incretin receptors (GLP-1R; GIPR) and other G-protein coupled receptors with great potential. With regards to therapy monitoring, the most commonly used criteria are Response Criteria Evaluation in Solid Tumors (RECIST). However, for different reasons, these criteria are not very useful in NET. Incorporation of other criteria such as Choi as well as functional imaging assessment with PET would be of great interest in this area.

  • 32.
    Cunningham, Janet Lynn
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Grimelius, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Genetics and Pathology.
    Sundin, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology.
    Agarwal, Smriti
    Christian Medical College, Vellore, India.
    Janson, Eva Tiensuu
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Malignant ileocaecal serotonin-producing carcinoid tumours: the presence of a solid growth pattern and/or Ki67 index above 1% identifies patients with a poorer prognosis2007In: Acta Oncologica, ISSN 0284-186X, E-ISSN 1651-226X, Vol. 46, no 6, p. 747-756Article in journal (Refereed)
    Abstract [en]

    Patients with malignant serotonin-producing carcinoid tumours in the jejunum, ileum and caecum generally have long survival expectancy. In some patients, however, tumour progression is more rapid and there is a need to identify them at an early stage. The purpose of this study was to determine if histopathological characteristics and/or Ki67 and apoptotic indices are of prognostic value in cases of metastatic disease. Eighty-one patients with this tumour were included in the study; all had metastases and their survival range was 1-223 months. Five growth patterns were identified and described. For 57 patients whose tumour material was available, the Ki67 and apoptotic indices were calculated for ten randomly selected tumour areas and 'hot spots'. A Cox regression analysis was used to test if histopathology and/or Ki67 index ≥1% could identify patients whose survival might be shorter than anticipated. One of the histopathological growth patterns-the solid (non-organoid) cell pattern-was correlated to shorter survival in both primary tumours and metastases, when compared with the organoid growth patterns (hazard ratio 2.9 and 2.3, p≤0.01). In 75% of primary tumours and 67% of metastases, the average Ki67 index was<0.5%. Ki67 index in 'hot spots' ranged from 0.1 to 14%. Ki67 index ≥1%, in both primary tumour and metastases, identified patients at increased risk of shorter survival (hazard ratio 5.4 and 2.5, p≤0.01). The apoptotic index was very low in all cases. We conclude that in patients with metastazising serotonin-producing carcinoids, two independent criteria, a solid growth pattern and Ki67 index ≥1%, can be used to identify patients with a poorer prognosis. This study also showed that Ki67 index <2% cannot, as previously suggested, be used to indicate a benign progression for this tumour category.

  • 33.
    Dam, G.
    et al.
    Aarhus Univ Hosp, Neuroendocrine Tumor Ctr Excellence, Dept Hepatol & Gastroenterol, Aarhus, Denmark.
    Grønbæk, H.
    Aarhus Univ Hosp, Neuroendocrine Tumor Ctr Excellence, Dept Hepatol & Gastroenterol, Aarhus, Denmark.
    Sørbye, H.
    Haukeland Hosp, Dept Oncol, Bergen, Norway.
    Thiis-Evensen, E.
    Natl Hosp Norway, Oslo Univ Hosp, Dept Transplantat Med, Neuroendocrine Tumor Ctr Excellence, Oslo, Norway.
    Paulsson, B.
    Novartis Sverige AB, Täby, Sweden.
    Sundin, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Jensen, C.
    Rigshosp, Neuroendocrine Tumor Ctr Excellence, Dept Radiol, Copenhagen, Denmark.
    Ebbesen, D.
    Aarhus Univ Hosp, Neuroendocrine Tumor Ctr Excellence, Dept Radiol, Aarhus, Denmark.
    Knigge, U.
    Rigshosp, Neuroendocrine Tumor Ctr Excellence, Dept Endocrinol, Copenhagen, Denmark.;Rigshosp, Neuroendocrine Tumor Ctr Excellence, Dept Surg Gastroenterol, Copenhagen, Denmark.
    Tiensuu Janson, Eva
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Endocrin Oncology.
    A Prospective Nordic Study on the Use of Chromogranin A for the Prediction of Progression in Patients with Pancreatic and Small Intestinal Neuroendocrine Tumors2018In: Neuroendocrinology, ISSN 0028-3835, E-ISSN 1423-0194, Vol. 106, no Supplement: 1, p. 152-152Article in journal (Other academic)
  • 34.
    Dam, Gitte
    et al.
    Aarhus Univ Hosp, Dept Gastroenterol & Hepatol, Neuroendocrine Tumour Ctr Excellence, DK-8200 Aarhus N, Denmark..
    Gronbaek, Henning
    Aarhus Univ Hosp, Dept Gastroenterol & Hepatol, Neuroendocrine Tumour Ctr Excellence, DK-8200 Aarhus N, Denmark..
    Sorbye, Halfdan
    Haukeland Hosp, Dept Oncol, Bergen, Norway.;Univ Bergen, Clin Sci, Bergen, Norway..
    Evensen, Espen Thiis
    Oslo Univ Hosp, Rigshosp, Dept Transplantat Med, Neuroendocrine Tumor Ctr Excellence, Oslo, Norway..
    Paulsson, Bjorn
    Novartis Sverige AB, Kista, Sweden..
    Sundin, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology. Uppsala Univ Hosp, Neuroendocrine Tumor Ctr Excellence, Uppsala, Sweden..
    Jensen, Claus
    Rigshosp, Neuroendocrine Tumour Ctr Excellence, Dept Radiol, Copenhagen, Denmark..
    Ebbesen, Dyveke
    Aarhus Univ Hosp, Neuroendocrine Tumour Ctr Excellence, Dept Radiol, Aarhus, Denmark..
    Knigge, Ulrich
    Rigshosp, Neuroendocrine Tumour Ctr Excellence, Dept Endocrinol, Copenhagen, Denmark.;Rigshosp, Neuroendocrine Tumour Ctr Excellence, Dept Surg Gastroenterol, Copenhagen, Denmark..
    Tiensuu Janson, Eva
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Endocrine Oncology.
    Prospective Study of Chromogranin A as a Predictor of Progression in Patients with Pancreatic, Small-Intestinal, and Unknown Primary Neuroendocrine Tumors2020In: Neuroendocrinology, ISSN 0028-3835, E-ISSN 1423-0194, Vol. 110, no 3/4, p. 217-224Article in journal (Refereed)
    Abstract [en]

    Background: Retrospective studies are conflicting but most of them report that an increase in plasma chromogranin A (CgA) predicts tumor progression in neuroendocrine tumor (NET) patients. Prospectively, we investigated if a change in plasma CgA is associated with tumor burden changes in NET patients with disseminated disease. Methods: We included 239 patients treated at 5 NET centers from December 2010 to December 2013. CgA was measured within 6 weeks of a CT or MRI in a patient undergoing at least 2 scan examinations performed over a period of 1-24 months. In a post hoc analysis, CgA measured 3-6 months prior to the CT/MRI was analyzed. Changes in tumor size were evaluated by RECIST1.1. A 25% change in CgA was chosen to discriminate between increased, decreased, or unchanged levels. Results: In 671 events (2 CT/MRI scans and 2 corresponding CgA measurements), we found a weak positive correlation between the RECIST 1.1 responses and change in plasma CgA from baseline (Spearman's rank correlation coefficient: 0.15; p < 0.05). Of 304 events in the post hoc analysis, 58 showed progression, 228 showed stable disease, and 18 showed regression, with a median change in CgA of 19% (IQR: 57 to -20%), -12% (23 to -38%), and -73% (-55 to -83%), respectively. The correlation coefficient for all sites was 0.17 (p = 0.003), and it was 0.16 (p = 0.07), 0.18 (p = 0.04), and 0.20 (p = 0.21) for small-intestinal (n = 137), pancreatic (n = 123), and unknown primary NET (n = 40), respectively. In the 58 patients showing tumor progression, the sensitivity and specificity of an increased CgA concentration were 36 and 82%, respectively, with positive and negative predictive values of 32 and 85%. Conclusions: In this prospective study of gastroenteropancreatic NET patients, we observed only a weak association between a change in plasma CgA and changes in tumor burden. CgA as a single biomarker was thus inadequate to predict tumor progression.

  • 35.
    Dam, Gitte
    et al.
    Department of Hepatology & Gastroenterology, ENETS Center of Excellence, Aarhus University Hospital, & Department of Clinical Medicine, Aarhus University, Aarhus, Denmark..
    Grønbæk, Henning
    Department of Hepatology & Gastroenterology, ENETS Center of Excellence, Aarhus University Hospital, & Department of Clinical Medicine, Aarhus University, Aarhus, Denmark..
    Sundlöv, Anna
    Division of Oncology, Department of Clinical Sciences Lund, Lund University, Sweden..
    Botling, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology.
    Sundin, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Petersen, Rene Horsleben
    Department of Cardiothoracic Surgery, ENETS Center of Excellence, Copenhagen University Hospital, Rigshospitalet, Denmark;f Department of Clinical Medicine, University of Copenhagen, Denmark..
    Welin, Staffan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Endocrine Oncology. Department of Clinical Physiology and Nuclear Medicine, ENETS Center of Excellence & Cluster for Molecular Imaging, Copenhagen University Hospital–Rigshospitalet..
    Evensen, Espen-Thiis
    Department for Organ Transplantation, Oslo University Hospital, ENETS Center of Excellence, Rikshospitalet, Oslo, Norway..
    Sorbye, Halfdan
    Department of Oncology, Haukeland University Hospital, and Department of Clinical Science, University of Bergen, Bergen, Norway..
    Tabaksblat, Elizaveta
    Department of Oncology, ENETS Center of Excellence, Aarhus University Hospital, Aarhus, Denmark..
    Arveschoug, Anne Kirstine
    Department of Nuclear Medicine & PET Center, Aarhus University Hospital, ENETS Center of Excellence, Aarhus, Denmark..
    Mortensen, Jann
    Department. of Clinical Physiology and Nuclear Medicine, ENETS Center of Excellence & Cluster for Molecular Imaging, Copenhagen University Hospital–Rigshospitalet.; Department of Biomedical Sciences, University of Copenhagen, Denmark..
    Kjaer, Andreas
    Department. of Clinical Physiology and Nuclear Medicine, ENETS Center of Excellence & Cluster for Molecular Imaging, Copenhagen University Hospital–Rigshospitalet.; Department of Biomedical Sciences, University of Copenhagen, Denmark..
    Knigge, Ulrich
    Departments of Gastrointestinal Surgery and Clinical Endocrinology, ENETS Center of Excellence, Copenhagen University Hospital, Rigshospitalet, Denmark..
    Tiensuu Janson, Eva
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Endocrine Oncology.
    Langer, Seppo W.
    Department of Oncology, ENETS Center of Excellence, Copenhagen University Hospital, Rigshospitalet, and Dept. of Clinical Medicine, University of Copenhagen, Denmark..
    Nordic 2023 guidelines for the diagnosis and treatment of lung neuroendocrine neoplasms.2023In: Acta Oncologica, ISSN 0284-186X, E-ISSN 1651-226X, Vol. 62, no 5, p. 431-437Article in journal (Refereed)
    Abstract [en]

    Lung neuroendocrine neoplasms (NEN) are a heterogeneous population of neoplasms with different pathology, clinical behavior, and prognosis compared to the more common lung cancers. The diagnostic work-up and treatment of patients with lung- NEN has undergone major recent advances and new methods are currently being introduced into the clinic. These Nordic guidelines summarize and update the Nordic Neuroendocrine Tumor Group's current view on how to diagnose and treat lung NEN-patients and are meant to be useful in the daily practice for clinicians handling these patients. This review reflects our view of the current state of the art of diagnosis and treatment of patients with lung-NEN. Small cell lung carcinoma (SCLC) is not included in these guidelines.

  • 36. de Herder, Wouter W
    et al.
    Capdevila, Jaume
    Unmet Needs in the Field of Neuroendocrine Neoplasms of the Gastrointestinal Tract, Pancreas, and Respiratory System: Reports by the ENETS Group.2019In: Neuroendocrinology, ISSN 0028-3835, E-ISSN 1423-0194, Vol. 108, no 1, p. 5-6Article in journal (Refereed)
    Abstract [en]

    On the 10th and 11th of November 2016, 54 international experts in the field of neuroendocrine neoplasms (NEN) of the gastrointestinal tract, pancreas, and respiratory system met in Munich, Germany, to discuss and determine unmet needs in this field. The participating experts were Advisory Board members and invited guests of the European Neuroendocrine Tumor Society (ENETS). The Board members were medical specialists with different clinical or preclinical backgrounds, basic scientists, specialized nurses, and patient representatives.

    According to the Oxford dictionary, “unmet” refers to something (here, a need) which has not been achieved or fulfilled. The NEN expert subgroups succeeded in producing 6 reports on what they identified as the most relevant unmet needs in NEN. They identified several limitations of the current tumor classification, grading, and staging systems for almost all NEN subtypes.

    Apart from the historical separation regarding origin into foregut, midgut, and hindgut, other subentities have now been recognized, each requiring a more tailored approach. There is still a general lack of predictive and prognostic markers, in samples of both tumor tissue and surrogate tissues such as the blood. Tumor visualization making use of radiology and nuclear medicine has seen impressive advances in recent years. However, with regard to determining tumor (metastases) responses, there is still debate as to how best to achieve this with different imaging modalities.

    In spite of more treatment options (locoregional and systemic) being available for metastatic NENs, help is needed to select appropriate treatment strategies (sequencing) and there is also a need for more effective treatments. For some tumor entities, watchful waiting might be considered (e.g., in the case of small pancreatic NENs) but, again, the lack of reliable markers makes it difficult to decide which tumors should undergo resection and which should be monitored only. There are currently no registered or approved adjuvant treatment options for the period after curative resection of some of the isolated or locally advanced NENs (e.g., of the pancreas, appendix, and rectum). It is also unclear which patients might benefit from adjuvant treatment. The follow-up of patients with NENs remains a poorly studied area and is based on loose empirical international guidelines or institutional opinion.

    All of these unmet needs in the field of NENs exponentially increase the complexity of conducting well-designed clinical and translational studies to resolve these issues, with multidisciplinary and international efforts such as the current one led by ENETS being the only way to move forward. We invite all Readers of Neuroendocrinology interested in the field of NENs to study the series of 6 articles reporting on unmet needs in the field of NENs

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  • 37.
    Delle Fave, G.
    et al.
    Osped St Andrea, Dept Digest & Liver Dis, Rome, Italy.;Univ Roma La Sapienza, Dept Digest & Liver Dis, Via Grottarossa 1035, IT-00189 Rome, Italy..
    O'Toole, D.
    St Vincents Univ, NET Ctr, Dublin, Ireland.;St James Hosp, Dept Clin Med, Dublin 8, Ireland.;Univ Dublin Trinity Coll, Dublin 2, Ireland..
    Sundin, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Taal, B.
    Netherlands Canc Ctr, Lijnden, Netherlands..
    Ferolla, P.
    Univ Perugia, Umbria Reg Canc Network, NET Ctr, I-06100 Perugia, Italy..
    Ramage, J. K.
    Hampshire Hosp NHS Trust, Dept Gastroenterol, Winchester, Hants, England..
    Ferone, D.
    Univ Genoa, Dept Endocrine & Metab Sci, Genoa, Italy..
    Ito, T.
    Kyushu Univ Hosp, Pancreat Dis Branch, Fukuoka 812, Japan..
    Weber, W.
    Mem Sloan Kettering Canc Ctr, Dept Radiol, 1275 York Ave, New York, NY 10021 USA..
    Zheng-Pei, Z.
    Beijing Union Med Coll Hosp, Dept Endocrinol, Beijing, Peoples R China..
    De Herder, W. W.
    Erasmus MC, Div Endocrinol, Dept Internal Med, Rotterdam, Netherlands..
    Pascher, A.
    Charite, Dept Visceral & Transplant Surg, Campus Virchow Klinikum, D-13353 Berlin, Germany..
    Ruszniewski, P.
    Beaujon Hosp, Dept Gastroenterol, Clichy, France..
    ENETS Consensus Guidelines Update for Gastroduodenal Neuroendocrine Neoplasms2016In: Neuroendocrinology, ISSN 0028-3835, E-ISSN 1423-0194, Vol. 103, no 2, p. 119-124Article in journal (Refereed)
  • 38. Dogra, Prerna
    et al.
    Sundin, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology. Molecular Imaging, Uppsala University Hospital.
    Juhlin, C. Christofer
    Calissendorff, Jan
    Falhammar, Henrik
    Bancos, Irina
    Rare benign adrenal lesions2023In: European Journal of Endocrinology, ISSN 0804-4643, E-ISSN 1479-683X, Vol. 188, no 4, p. 407-420Article in journal (Refereed)
    Abstract [en]

    While most benign lesions of the adrenal glands represent either an adrenocortical adenoma or a myelolipoma, the advent and frequent use of high-resolution radiological investigations have led to relatively increased incidental discovery of rare adrenal lesions, specifically benign adrenal cysts, adrenal ganglioneuromas, adrenal schwannomas, adrenal hemorrhage, and adrenal calcifications. Radiological characteristics of the different rare benign adrenal lesions could vary from distinct to indeterminate. Though typically nonfunctional, these rare lesions require evaluation for adrenal hormone excess, as they may phenotypically appear similar to pheochromocytoma or adrenocortical carcinoma and could sometimes be associated with or conceal an underlying functional adrenal tumor. In this review, we discuss the various rare benign adrenal lesions, emphasizing a practical perspective.

  • 39. Dromain, Clarisse
    et al.
    Sundin, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Najran, Pavan
    Vidal Trueba, Hector
    Dioguardi Burgio, Marco
    Crona, Joakim
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Endocrine Tumor Biology.
    Opalinska, Marta
    Carvalho, Luciana
    Franca, Regis
    Borg, Philip
    Vietti Violi, Naik
    Schaefer, Niklaus
    Lopez, Carlos
    Pezzutti, Daniela
    de Mestier, Louis
    Lamarca, Angela
    Costa, Frederico
    Pavel, Marianne
    Ronot, Maxime
    Tumour Growth Rate to predict the outcome of patients with Neuroendocrine Tumours: Performance and sources of variability2021In: Neuroendocrinology, ISSN 0028-3835, E-ISSN 1423-0194, Vol. 111, no 9, p. 831-839Article in journal (Refereed)
    Abstract [en]

    INTRODUCTION: Tumor growth rate (TGR), percentage of change in tumor volume/month, has been previously identified as an early radiological biomarker for treatment monitoring in neuroendocrine tumors (NETs) patients. We assessed the performance and reproducibility of TGR 3 months (TGR3m) as a predictor factor of progression-free survival (PFS), including the impact of imaging method and reader variability.

    METHODS: Baseline and 3-months (±1month) CT/MRI images from patients with advanced, grade 1-2 NETs were retrospectively reviewed by 2 readers. Influence of number of targets, tumor burden and location of lesion on the performance of TGR3m to predict PFS was assessed by uni/multivariable Cox regression analysis. Agreement between readers was assessed by the Lin's concordance coefficient (LCC) and Kappa (KC).

    RESULTS: A total of 790 lesions were measured in 222 patients. Median PFS was 22.9 months. On univariable analysis, number of lesions (</≥4), tumor burden and presence of liver metastases were significantly correlated to PFS. On multivariate analysis, ≥4 lesions (HR:1.89 (95%CI:1.01-3.57)), TGR3m ≥0.8%/m (HR:4.01 (95%CI:2.31-6.97)) and watch-and-wait correlated with shorter PFS. No correlation was found between TGR3m and number of lesions (rho:-0.2; p-value:0.1930). No difference in mean TGR3m across organs was shown (p-value:0.6). Concordance between readers was acceptable (LCC:0.52 (95%CI:0.38-0.65); KC:0.57 agreement:81.55%). TGR3m remained a significant prognostic factor when data from second reader was employed (HR:4.35 (95%CI:2.44-7.79); p-value<0.001) and regardless his expertise (HR:1.21 (95%CI:0.70-2.09); p-value:0.493).

    DISCUSSION/CONCLUSION: TGR3m is a robust and early radiological biomarker able to predict PFS. It may be used to identify patients with advanced NETs who require closer radiological follow-up.

  • 40.
    Dromain, Clarisse
    et al.
    Lausanne Univ Hosp, Dept Radiol, CH-1011 Lausanne, Switzerland.;Univ Lausanne, CH-1011 Lausanne, Switzerland.
    Vullierme, Marie-Pierre
    Univ Paris, Hop Univ Paris Nord Val Seine, Hop Beaujon, Dept Radiol, Paris, France.
    Hicks, Rodney J.
    Univ Melbourne, Peter MacCallum Canc Ctr, Neuroendocrine Serv, Melbourne, Vic, Australia.;Univ Melbourne, Sir Peter MacCallum Dept Oncol, Melbourne, Vic, Australia.
    Prasad, Vikas
    Univ Ulm, Dept Nucl Med, Ulm, Germany.
    O'Toole, Dermot
    St Jamess & St Vincents Univ Hosp, Dublin, Ireland.;Trinity Coll Dublin, Dublin, Ireland.
    de Herder, Wouter W.
    Erasmus MC, Dept Internal Med, Sect Endocrinol, Rotterdam, Netherlands..
    Pavel, Marianne
    Univ Klinikum Erlangen, Dept Med 1, Erlangen, Germany.
    Faggiano, Antongiulio
    Sapienza Univ Rome, St Andrea Hosp, Dept Clin & Mol Med Sapienza, Rome, Italy.
    Kos-Kudla, Beata
    Med Univ Silesia, Dept Endocrinol & Neuroendocrine Tumors, Katowice, Poland.
    Öberg, Kjell
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Endocrine Tumor Biology.
    Krejs, Guenter J.
    Med Univ Graz, Dept Internal Med, Div Gastroenterol & Hepatol, Graz, Austria.
    Grande, Enrique
    MD Anderson Canc Ctr Madrid, Dept Med Oncol, Madrid, Spain.
    Niederle, Bruno
    Med Univ Vienna, Dept Gen Surg, Vienna, Austria.
    Sundin, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    ENETS standardized (synoptic) reporting for radiological imaging in neuroendocrine tumours2022In: Journal of neuroendocrinology, ISSN 0953-8194, E-ISSN 1365-2826, Vol. 34, no 3 SI, article id 13044Article in journal (Refereed)
    Abstract [en]

    This expert consensus document represents an initiative by the European Neuroendocrine Tumor Society (ENETS) to provide guidance for synoptic reporting of radiological examinations critical to the diagnosis, grading, staging and treatment of neuroendocrine neoplasms (NENs). Template drafts for initial tumor staging and follow-up by computed tomography (CT) and magnetic resonance imaging (MRI) were established, based on existing institutional and organisational reporting templates relevant for NEN imaging, and applying the RadLex lexicon of radiological information (Radiological Society of North America), for consistency regarding the radiological terms. During the ENETS Scientific Advisory Board meeting 2018, the template drafts were subject to iterative interdisciplinary discussions among experts in imaging, surgery, gastroenterology, oncology and pathology. Members of the imaging group stated a strong preference for a combination of limited and standardised options by way of drop-down menus. Separate templates were produced for the initial work-up and for follow-up, respectively. To provide a detailed description of the radiological findings of the primary tumor and its local extension and spread, different templates were developed for bronchial, pancreatic and gastrointestinal NENs for CT and MRI, respectively. Each template was structured in 10 sections: clinical details, comparative imaging modality, acquisition technique, primary tumor findings, regional lymph node metastases, distant metastases, TNM classification, reference lesions according to RECIST 1.1, additional findings and conclusion. Two templates were developed for follow-up, for CT and MRI, respectively, and were specifically focused on assessment of therapy response. These included a qualitative response assessment, such as decrease of vascularisation and presence of necrosis, and a quantitative assessment according to RECIST 1.1 and the modified RECIST (mRECIST) for assessing tumor response following transarterial chemoembolisation.

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  • 41.
    Edgren, Maliha
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology, Oncology.
    Westlin, J E
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology, Oncology.
    Kälkner, K M
    Sundin, Anders
    Nilsson, Sven
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology, Oncology.
    [111In-DPTA-D-Phe1] - Octreotide Scintigraphy in the Management of Patients with Advanced Renal Cell Carcinoma1999In: Cancer Biotherapy and Radiopharmaceuticals, ISSN 1084-9785, E-ISSN 1557-8852, Vol. 14, no 1, p. 59-64Article in journal (Other academic)
    Abstract [en]

    Somatostatin receptor scintigraphy using the 111In-labelled somatostatin analogue octreotide (Octreoscan) was performed in 9 patients with metastatic renal cell carcinoma. In total 11 scintigraphies were performed. Positive tumor uptakes were observed in 9 patients. The results of the octreotide scans were correlated to diagnostic CT and/or X-ray images. Forty (59%) out of 68 known tumor localizations were visualized with the octreotide scan. A second scan following therapy was performed in two patients. These patients showed progressive disease despite treatment and also exhibited intensified uptakes at octreotide scintigraphy. One false positive lesion was observed in the 40 lesions visualized in scintigraphy.

    It was concluded that renal cell carcinoma expresses somatostatin receptors, as could be visualized with Octreoscan scintigraphy. The scintigraphic technique can be used as an instrument for in vivo characterization of the disease. The data could also form a basis for future investigations regarding the possible therapeutic effect of octreotide in the management of renal cell cancer.

  • 42.
    Eich, Torsten
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology.
    Eriksson, Olof
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology.
    Sundin, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology.
    Estrada, Sergio
    Brandhorst, Daniel
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology.
    Brandhorst, Heide
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology.
    Långström, Bengt
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Biochemistry and Organic Chemistry.
    Nilsson, Bo
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology.
    Korsgren, Olle
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology.
    Lundgren, Torbjörn
    Positron emission tomography: A real-time tool to quantify early islet engraftment in a preclinical large animal model2007In: Transplantation, ISSN 0041-1337, E-ISSN 1534-6080, Vol. 84, no 7, p. 893-898Article in journal (Refereed)
    Abstract [en]

    Background. Clinical islet transplantation is currently being explored as a therapeutic option for persons with type I diabetes and hypoglycemic unawareness. Techniques to monitor graft survival are urgently needed to optimize the procedure. Therefore, the objective of the present study was to develop a technique for imaging survival of transplanted islets in the peritransplant and early posttransplant phase.

    Methods. Isolated porcine islets were labeled in vitro with 2-deoxy-2[18F]fluoro-D-glucose ([18F]FDG) and infused intraportally into anesthetized pigs (n=10). Dynamic examination was performed on a positron emission tomography/computed tomography hybrid system.

    Results. More than 95% of the radioactivity was confined to the islets at the time of transplantation. The peak percentage of infused radioactivity within the liver, quantified at the end of the islet infusion, was only 54±5.1%. The distribution of the radioactivity in the liver was found to be heterogeneous. A whole-body examination showed no accumulation in the lungs or brain; extrahepatic radioactivity was, except urinary excretion, evenly distributed in the pig body.

    Conclusions. Our results imply that almost 50% of the islets were damaged to the extent that the FDG contained was release within minutes after intraportal transplantation. The distribution of radioactivity without accumulation in the brain indicates that the activity is released from lysed islet cells in the form of [18F]FDG-6P rather than native [18F]FDG. The presented technique shows promise to become a powerful and quantitative tool, readily available in the clinic, to evaluate initial islet engraftment and survival.

  • 43.
    Ekberg, Tomas
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Otolaryngology and Head and Neck Surgery.
    Sörensen, Jens
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Engström, Mats
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Otolaryngology and Head and Neck Surgery.
    Blomquist, Erik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology, Oncology.
    Sundin, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology, Radiology.
    Anniko, Matti
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Otolaryngology and Head and Neck Surgery.
    Clinical impact of positron emission tomography (PET) with (18F)fluorodeoxyglucose (FDG) in head and neck tumours2007In: Acta Oto-Laryngologica, ISSN 0001-6489, E-ISSN 1651-2251, Vol. 127, no 2, p. 186-193Article in journal (Refereed)
    Abstract [en]

    Conclusion. PET plays an important role in staging, on suspicion of recurrence and for detection of occult primary tumours in the head and neck. Objective: Since 1998 we have used positron emission tomography (PET) with (F-18)fluorodeoxyglucose (FDG) to assess selected patients. This procedure has often helped in making decisions on staging and treatment. Patients and methods. The case records of the first 80 patients (104 PET examinations) were studied retrospectively. Results. A total of 39 examinations were performed for staging. PET detected all primary tumours except two (stage T1), and staging was adjusted after 13%. In all, 33 PET examinations were performed on suspicion of recurrent tumour. In 52% of these PET determined further treatments; in 21% PET had a direct impact on the surgical planning. In 18 patients with metastases from an occult primary tumour, PET detected 39% of those tumours; in 22% it was the sole modality to do so. No recurrences or second primary tumours were detected when PET was used for follow-up of clinically cured patients. Results were similar when squamous cell carcinomas (SCCs) were considered alone as compared to the complete material. The mean standardized uptake value (SUV) was higher for cases deemed tumour-positive than in negative cases.

  • 44.
    Ekeblad, Sara
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Sundin, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology.
    Janson, Eva Tiensuu
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Welin, Staffan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Granberg, Dan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Kindmark, Henrik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Dunder, Kristina
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Kozlovacki, Gordana
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Örlefors, Håkan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Sigurd, Mattias
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Öberg, Kjell
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Eriksson, Barbro
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Skogseid, Britt
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Temozolomide as monotherapy is effective in treatment of advanced malignant neuroendocrine tumors2007In: Clinical Cancer Research, ISSN 1078-0432, E-ISSN 1557-3265, Vol. 13, no 10, p. 2986-2991Article in journal (Refereed)
    Abstract [en]

    Purpose: A retrospective analysis of the toxicity and efficacy of temozolomide in advanced neuroendocrine tumors. Experimental Design: Thirty-six patients with advanced stages of neuroendocrine tumor (1 gastric, 7 thymic and 13 bronchial carcinoids, 12 pancreatic endocrine tumors, 1 paraganglioma, 1 neuroendocrine foregut, and 1 neuroendocrine cecal cancer) were treated with temozolomide (200 mg/m2) for 5 days every 4 weeks. Patients had previously received a mean of 2.4 antitumoral medical regimens. Tumor response was evaluated radiologically according to the Response Evaluation Criteria in Solid Tumors every 3 months on an intent-to-treat basis. The circulating tumor marker plasma chromogranin A was also assessed. The expression of 06-methylguanine DNA methyltransferase, an enzyme implicated in chemotherapy resistance, was studied by immunohistochemistry (n = 23) and compared with response to temozolomide. Results: Median overall time to progression was 7 months (95% confidence interval, 3-10). Radiologic response was seen in 14% of patients and stable disease in 53%. Side effects were mainly hematologic; 14% experienced grade 3 or 4 thrombocytopenia (National Cancer Institute toxicity criteria). Ten patients had tumors with 06-methylguanine DNA methyltransferase immunoreactivity in <10% of nuclei, whereas four patients showed radiologic responses. Conclusions: Temozolomide as monotherapy had acceptable toxicity and antitumoral effects in a small series of patients with advanced malignant neuroendocrine tumors and four of these showed radiologic responses.

  • 45. Eriksson, B
    et al.
    Örlefors, Håkan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiovascular epidemiology.
    Sundin, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Section of Nuclear Medicine and PET.
    Westlin, J E
    Bergström, Mats
    Långström, Bengt
    Öberg, Kjell
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Endocrine Oncology.
    [PET in neuroendocrine tumors].1998In: Nordisk Medicin, ISSN 0029-1420, Vol. 113, no 9, p. 308-312Article in journal (Refereed)
    Abstract [sv]

    With the radionuclide tracers available today, 50-90 per cent of neuroendocrine tumours of the gastro-intestinal tract can be visualised with PET (positron-emission tomography). PET also enables the effect of tumour treatment to be monitored in terms of biochemical and functional variables, which is not possible with other radiological techniques. Owing to the very good tumour resolution possible with PET, it serves as a complement to other routine methods such as computed tomography and ultrasonography, and can be used to screen the chest and abdomen for small primary tumours that can not be detected with other methods. In several pre-operative trials PET has been shown to demonstrate more changes in the pancreas and liver than was possible with other methods. In the near future it will be possible to demonstrate the presence of and quantify growth factor receptors, hormones, enzymes, DNA synthesis, mRNA synthesis and protein synthesis. Access to these tumour biological data will be of crucial importance to the individualisation of treatment.

  • 46.
    Eriksson, Barbro
    et al.
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Medical Sciences. Onkologisk endokrinologi.
    Bergström, M
    Örlefors, Håkan
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Medical Sciences. Onkologisk endokrinologi.
    Sundin, Anders
    Öberg, Kjell
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Medical Sciences. Onkologisk endokrinologi.
    Långström, B
    PET for clinical diagnosis and research in neuroendocrine tumors2003In: Diagn Nuclear Medicine 4th edition, 2003, p. 747-754Chapter in book (Refereed)
  • 47.
    Eriksson, Barbro
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Endocrine Tumor Biology.
    Bergström, Mats
    Sundin, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Juhlin, Claes
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Örlefors, Håkan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Endocrine Oncology.
    Öberg, Kjell
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Endocrine Oncology. onk endo.
    Långström, Bengt
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Section of Nuclear Medicine and PET.
    The role of PET in localization of neuroendocrine and adrenocortical tumors2002In: Annals of the New York Academy of Sciences, ISSN 0077-8923, E-ISSN 1749-6632, Vol. 970, p. 159-169Article in journal (Refereed)
    Abstract [en]

    Positron emission tomography (PET) supplies a range of labeled compounds to be used for the characterization of tumor biochemistry. Some of these have proved to be of value for clinical diagnosis, treatment follow up, and clinical research. The first routinely used PET tracer in oncology, 18F-labeled deoxyglucose (FDG), was successfully used for diagnosis of cancer, reflecting increased expression of glucose transporter in cancerous tissue. This tracer, however, usually does not show sufficient uptake in well-differentiated tumors such as neuroendocrine tumors. We developed a tracer more specific to neuroendocrine tumors—the serotonin precursor 5-hydroxytryptophan (5-HTP) labeled with 11C—and demonstrated increased uptake and irreversible trapping of this tracer in carcinoid tumors. The uptake was so selective and the resolution was so high that we could detect more liver and lymph node metastases with PET than with CT or octreotide scintigraphy. To further improve the method, especially to reduce the high renal excretion of the tracer producing streaky artifacts in the area of interest, we introduced premedication by the decarboxylase inhibitor carbidopa, leading to a six-fold decreased renal excretion while the tumor uptake increased three-fold, hence improving the visualization of the tumors.

    11C-labeled l-DOPA was evaluated as an alternative tracer, especially for endocrine pancreatic tumors, which usually do not demonstrate enhanced urinary serotonin metabolites. However, only half of the EPTs, mainly functioning tumors, could be detected with l-DOPA. Instead 5-HTP seems to be a universal tracer for EPT and foregut carcinoids. With new, more sensitive PET cameras, larger field of view and procedures for whole-body coverage, the PET examination with 5-HTP is now routinely performed as reduced whole-body PET examinations with coverage of the thorax and abdomen. With this method we have been able to visualize small neuroendocrine lesions in the pancreas and thorax (e.g., ACTH-producing bronchial carcinoids) not detectable by any other method, including octreotide scintigraphy, MRI, and CT. Another tracer, the 11β-hydroxylase inhibitor, metomidate labeled with 11C, was developed to simplify diagnosis and follow-up of patients with incidentalomas. A large series of patients with incidentally found adrenal masses have been investigated and so far all lesions of adrenocortical origin have been easily identified because of exceedingly high uptake of 11C-metomidate, whereas noncortical lesions showed very low uptake. In addition, adrenocortical cancer shows high uptake, suggesting that this PET tracer can be used for staging purposes.

  • 48.
    Eriksson, Barbro
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Bergström, Mats
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Section of Nuclear Medicine and PET.
    Örlefors, Håkan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Sundin, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology.
    Öberg, Kjell
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences. Endokrin onkologi.
    Långström, Bengt
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Medicinal Chemistry, Preclinical PET Platform.
    Use of PET in neuroendocrine tumors: In vivo applications and in vitro studies2000In: The Quarterly journal of nuclear medicine, ISSN 1125-0135, Vol. 44, no 1, p. 68-76Article in journal (Refereed)
    Abstract [en]

    Positron emission tomography (PET) performed with various radiolabelled compounds facilitates the study of tumor biochemistry. If the tumor uptake of an administered tracer is greater than that of surrounding normal tissue, it is also possible to localize the tumor. In initial studies, 18F-labeled deoxyglucose (FDG) was attempted to visualize the tumors, since this tracer had been successfully used in oncology, reflecting increased glucose metabolism in cancerous tissue. However, this tracer was not to any significant degree taken up by the neuroendocrine tumors. Instead, the serotonin precursor 5-hydroxytryptophan (5-HTP) labeled with 11C was used and showed an increased uptake and irreversible trapping of this tracer in carcinoid tumors. The uptake was selective and the resolution so high that we could detect more liver and lymph node metastases with PET than with CT or octreotide scintigraphy. One problem was, however, the high renal excretion of the tracer producing streaky artifacts in the area of interest. Using the decarboxylase inhibitor carbidopa, given as peroral premedication, the renal excretion decreased 6-fold and at the same time the tumor uptake increased 3-fold, hence improving the visualization of the tumors. When patients were followed during treatment with PET using 5-HTP as a tracer, a > 95% correlation between changes in urinary 5-hydroxyindoleacetic acid (U-5-HIAA) and changes in the transport rate constant for 5-HTP was observed. Thus, PET can be used to monitor treatment effects. Elevation of U-5-HIAA is considered to be uncommon in endocrine pancreatic tumors (EPTs). Initially, 11C-labeled L-DOPA was attempted as another amine important in the APUD system. With L-DOPA about half of the EPTs, mainly functioning tumors, could be detected. Recently, 5-HTP was explored as a universal tracer also for EPT and foregut carcinoids, extending the PET-examination to both thorax and abdomen (whole-body PET-examination). With this method we were able to visualize small lesions in the pancreas and thorax (e.g. ACTH-producing bronchial carcinoids) not detectable by any other method including octreotide scintigraphy, MRI and CT. Several other tracers have been investigated, e.g. the monoamineoxidase (MAO-A) inhibitor harmine with promising results in non-functioning EPTs. We are currently exploring a wide range of biochemical systems, including enzymes and receptors, both for neurotransmitters and for peptides and proteins in in vitro assays with the potential to use some of the developed tracers for in vivo visualization and tumor biological studies. In conclusion, PET is a valuable tool in the diagnosis of neuroendocrine tumors. It can detect small lesions in the thorax and abdomen not detected by other methods, which has been of great value preoperatively in several cases. It detects more lesions in the liver and lymph nodes than other methods and furthermore, it can be used to monitor treatment effects.

  • 49.
    Eriksson, Barbro
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Endocrine Tumor Biology.
    Sundin, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Wassberg, Cecilia
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Skogseid, Britt
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Endocrine Tumor Biology.
    Antonodimitrakis, Pantelis
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Endocrine Tumor Biology.
    Streptozocin and 5-fluorouracil treatment of pancreatic neuroendocrine tumors: efficacy, toxicity and prognostic factors2014In: Wiener Klinische Wochenschrift, ISSN 0043-5325, E-ISSN 1613-7671, Vol. 126, no S3, p. S145-S145, article id FP7.1Article in journal (Other academic)
  • 50.
    Eriksson, Barbro
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Endocrine Tumor Biology.
    Örlefors, Håkan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiovascular epidemiology.
    Sundin, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Skogseid, Britt
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Endocrine Tumor Biology.
    Långstrom, Bengt
    Bergström, Mats
    Öberg, Kjell
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Endocrine Oncology.
    Positron emission tomography in neuroendocrine tumours1999In: The Italian Journal of Gastroenterology and Hepatology, ISSN 1125-8055, Vol. Suppl 2, p. S167-S171Article in journal (Refereed)
    Abstract [en]

    Positron emission tomography is an in vivo tracer and imaging technique that utilizes short-lived positron emitting radionuclides (11C, 15O, 13N, 18F) with half-lives ranging between 2 min and 2 hours. These radionuclides are interesting from the labelling viewpoint since they are natural constituents of most biologically active compounds. The short half-life is an advantage with regard to the irradiation dose to the patient but it is also a limitation since it requires the production of these radionuclides in close vicinity to the positron emission tomography camera.

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