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  • 101.
    Långström, Bengt
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Medicinal Chemistry, Preclinical PET Platform.
    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.
    Bergström, Mats
    [Positron emission tomography in oncology--an introduction]1998In: Nordisk Medicin, ISSN 0029-1420, Vol. 113, no 9, p. 299-300Article in journal (Refereed)
    Abstract [sv]

    Positron emission tomography has developed very much since the start in the late 1970s, especially with the development of new labelling procedures for PET-tracers. With the development of whole body imaging and the discovery that 18F-FDG allows a high sensitivity for the detection of soft tissue tumors, the clinical use has increased remarkably. The cost-effectiveness of this modality, when properly used, has been demonstrated and 18F-FDG-PET should be considered as an early alternative in patient evaluation.

  • 102.
    Mahteme, Haile
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences.
    Larsson, B S
    Sundin, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Graf, Wilhelm
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Colorectal Surgery.
    5-FU uptake in liver metastases after intravenous and intraperitoneal administration: an autoradiographic study in the rat1998In: Anticancer Research, ISSN 0250-7005, E-ISSN 1791-7530, Vol. 18, no 2A, p. 943-949Article in journal (Refereed)
    Abstract [en]

    AIM:

    To analyse 5-fluorouracil (5-FU) uptake in hepatic metastases and normal tissues after intravenous (i.v.), intraperitoneal (i.p.e.) and intraportal (IPO) administration.

    METHODS AND RESULTS:

    A total of 18 inbred rats with hepatic metastases were injected with 14C-labelled 5-FU either through the i.v. (n = 7), i.p.e (n = 7) or IPO (n = 4) route. Radioactivity was visualised autoradiographically and quantified by computer-based image analysis. After 20 minutes, 10 i.v. injected tumours showed a higher amount of radioactivity (mean +/- SD) 23.8 +/- 7.8 than 6 i.p.e. injected (16.5 +/- 5.1, P = 0.06). At 2 hours, 9 i.v. injected metastases contained more radioactivity (49.6 +/- 9.2) than 19 i.p.e. injected tumours (28.2 + 11.3, P = 0.00003). After 24 hours, 2 i.p.e. injected tumours had higher radioactivity (mean 25.2) compared with 7 i.v. injected (7.6 +/- 4.1). IPO administration did not confer higher radioactivity at any time point. When the calculations were based on average metastatic radioactivity of individual rats, the difference between i.v. and i.p.e. injected rats was still present at 2 hours.

    CONCLUSION:

    These results indicate that early tumour 5-FU uptake after intraperitoneal and intraportal administration may be inferior to that after intravenous injection. Deposition of the drug in the peritoneal cavity may, however, act as a slow release preparation giving continuous drug exposure for prolonged periods of time. These results suggest a role for combined intravenous and intraperitoneal adjuvant therapy.

  • 103.
    Mahteme, Haile
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences.
    Larsson, B
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmaceutical Biosciences, Toxicology.
    Sundin, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmaceutical Biosciences, Pharmaceutical Biochemistry.
    Khamis, Harry
    Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Social Sciences, Department of Information Science.
    Graf, Wilhelm
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences.
    Uptake of 5-fluorouracil (5-FU) in peritoneal metastases in relation to the route of drug administration and tumour debulking surgery: an autoradiographic study in the rat2004In: European Journal of Cancer, ISSN 0959-8049, E-ISSN 1879-0852, Vol. 40, no 1, p. 142-147Article in journal (Refereed)
    Abstract [en]

    Patients with peritoneal metastases from colorectal cancer have a poor prognosis. Aggressive treatment by debulking surgery and intraperitoneal (i.p.) chemotherapy has been suggested as an alternative therapy. However, the drug penetrance into the tumour in relation to the administration route and surgical reduction of the tumour is not well known. We compared locoregional administration with intravenous (i.v.) injection. Thirty-four in-bred rats with peritoneal metastases were randomly allocated into eight groups and injected with 14C-labelled 5-fluorouracil (5-FU) either through the i.v. or i.p. route, with or without a preceding tumour debulking, and were sacrificed after 2 or 8 h. Tumour radioactivity was visualised by autoradiography and quantified by a computer-based image analysis. After 8 h, 19 debulked and i.p.-injected tumours had a higher drug uptake, 63.2+/-28 (mean+/-standard deviation (SD)) kBq/g than 62 native i.p.-injected tumours (32.8+/-14) or 22 debulked and i.v.-injected tumours (18.5+/-18, P=0.002). After 8 h, 9 small tumours (<median 571 pixels) which underwent i.p. injection and tumour reduction had a higher drug uptake (77.4+/-26) than 29 non-debulked and i.p.-injected (35.1+/-17) or eight debulked and i.v. injected tumours (23.0+/-16, P=0.004). For larger tumours (>/=median 571 pixels), 16 debulked and i.p.-injected tumours had a higher radioactivity (drug uptake) (150.7+/-63) at 2 h than 49 i.p.-injected native tumours (48.5+/-59) or 11 reduced and i.v.-injected tumours (19.9+/-13, P=0.03). At 8 h, 10 debulked and i.p.-injected tumours had a higher drug uptake (50.3+/-24) than 33 native and i.p.-injected (30.8+/-10) or 14 debulked and i.v.-injected tumours (16.0+/-19, P=0.001). These results indicate that a debulking procedure and locoregional treatment of peritoneal metastases is associated with an increased level of 5-FU in the tumours.

  • 104.
    Mahteme, Haile
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences.
    Lövqvist, A
    Graf, Wilhelm
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Colorectal Surgery.
    Lundqvist, Hans
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Biomedical Radiation Sciences.
    Carlsson, Jörgen
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Biomedical Radiation Sciences.
    Sundin, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Adjuvant 131I-anti-CEA-antibody radioimmunotherapy inhibits the development of experimental colonic carcinoma liver metastases1998In: Anticancer Research, ISSN 0250-7005, E-ISSN 1791-7530, Vol. 18, no 2A, p. 843-848Article in journal (Refereed)
    Abstract [en]

    Adjuvant radioimmunotherapy (RIT) for human colonic cancer was performed in a nude rat model of experimental liver metastases. Thirty-three rats were injected intraportally through a mesenteric vein with 5 x 10(6) cells from the human colonic cancer cell line LS174T. Within half an hour, 20 MBq (n = 2), 75 MBq (n = 5), or 150 MBq (n = 10) of the 131I-labelled anti- carcinoembryonic antigen (CEA) monoclonal antibody (MAb) 38S1 was administered intravenously (i.v.), whereas control groups received either i.v. saline injections (n = 12) or 150 MBq of the irrelevant 131I-labelled MAb 79C (n = 4). Decay corrected whole-body data showed that more than 80% of the initially MAb-bound radioiodine was excreted during the first 2 weeks. Whole- body clearance and blood clearance of 131I-38S1 and 131I-79C were essentially similar. At sacrifice 5-7 weeks after administration, neither 20 MBq nor 75MBq 131I-38S1 significantly prevented the development of liver metastases. By contrast, with 150 MBq, no metastases formed in the animals treated with MAb 131I-38S1 or 131I-79C. A radiation induced effect on the haematopoietic system was found in the 150MBq dosage groups. It is concluded that the inhibition of tumour induction was not strictly dependent on a radiation dose delivered by a tumour-specific MAb. Since a non-tumour-specific 131I-MAb, in a smaller group of animals, proved equally efficacious in preventing tumour growth, the total body 131I dose was probably the major contributing factor.

  • 105.
    Mahteme, Haile
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Upper Abdominal Surgery.
    Sundin, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Larsson, Bengt
    Khamis, Harry
    Arow, Kiril
    Graf, Wilhelm
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Colorectal Surgery.
    5-FU uptake in peritoneal metastases after pretreatment with radioimmunotherapy or vasoconstriction: an autoradiographic study in the rat2005In: Anticancer Research, ISSN 0250-7005, E-ISSN 1791-7530, Vol. 25, no 2A, p. 917-922Article in journal (Refereed)
    Abstract [en]

    This study was conducted to test if tumour drug uptake could be increased in experimental colorectal cancer peritoneal metastases, by using pretreatment with peritoneal vasoconstriction or radioimmunotherapy. A total of 29 nude rats with peritoneal metastases were injected intraperitoneally (i.p.) with 14C-labelled 5-FU. The animals were randomly allocated to 5 groups. Six days prior to 5-FU, group I (control) received i.p. NaCl, group II was subjected to i.p. radioimmunotherapy (RIT) 131I-labelled anti-CEA monoclonal antibody (150 MBq) and group III received i.p. Norbormide 10 minutes before 5-FU. Two days prior to 5-FU group IV and V received i.p. NaCl (control) and RIT, respectively. 5-FU uptake was visualised with autoradiography and quantified by computer-based image analysis. Tumours in group III showed a higher uptake (mean+/-SD, 21.4+/-17) than in group I (11.8+/-10, p=0.04). This was also true when the analysis was restricted to larger tumours (> or = median 627 pixels) group III (23.2+/-19) vs. group I (11.8+/-7, p=0.002). Peritoneal tumours in group II were of smaller size (median area 308 pixels) than in group I (619 pixels), in group III (901 pixels), in group IV (769 pixels) and in group V (808 pixels). RIT decreased the tumour size whereas it did not affect 5-FU uptake. The uptake of 5-FU was potentiated by pretreating the animals with Norbormide. These results demonstrate that 5-FU uptake in experimental peritoneal metastases is increased when the peritoneal absorption of the drug is blocked using pretreatment with a vasoconstrictive agent. This principle may also be relevant when treating patients with colorectal cancer peritoneal metastases.

  • 106. Modlin, Irvin M.
    et al.
    Öberg, Kjell
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Chung, Daniel C.
    Jensen, Robert T.
    de Herder, Wouter W.
    Thakker, Rajesh V.
    Caplin, Martyn
    Delle Fave, Gianfranco
    Kaltsas, Greg A.
    Krenning, Eric P.
    Moss, Steven F.
    Nilsson, Ola
    Rindi, Guido
    Salazar, Ramon
    Ruszniewski, Philippe
    Sundin, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology, Radiology.
    Gastroenteropancreatic neuroendocrine tumours2008In: The Lancet Oncology, ISSN 1470-2045, E-ISSN 1474-5488, Vol. 9, no 1, p. 61-72Article, review/survey (Refereed)
    Abstract [en]

    Gastroenteropancreatic (GEP) neuroendocrine tumours (NETs) are fairly rare neoplasms that present many clinical challenges. They secrete peptides and neuroamines that cause distinct clinical syndromes, including carcinoid syndrome. However, many are clinically silent until late presentation with mass effects. Investigation and management should be highly individualised for a patient, taking into consideration the likely natural history of the tumour and general health of the patient. Management strategies include surgery for cure (which is achieved rarely) or for cytoreduction, radiological intervention (by chemoembolisation and radiofrequency ablation), chemotherapy, and somatostatin analogues to control symptoms that result from release of peptides and neuroamines. New biological agents and somatostatin-tagged radionuclides are under investigation. The complexity, heterogeneity, and rarity of GEP NETs have contributed to a paucity of relevant randomised trials and little or no survival increase over the past 30 years. To improve outcome from GEP NETs, a better understanding of their biology is needed, with emphasis on molecular genetics and disease modeling. More-reliable serum markers, better tumour localisation and identification of small lesions, and histological grading systems and classifications with prognostic application are needed. Comparison between treatments is currently very difficult. Progress is unlikely to occur without development of centers of excellence, with dedicated combined clinical teams to coordinate multicentre studies, maintain clinical and tissue databases, and refine molecularly targeted therapeutics.

  • 107.
    Mårs, Ulla
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmaceutical Biosciences.
    Tolmachev, Vladimir
    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.
    Positron emission tomography of experimental melanoma with [76Br]5-bromo-2-thiouracil2000In: Nuclear Medicine and Biology, ISSN 0969-8051, E-ISSN 1872-9614, Vol. 27, no 8, p. 845-9Article in journal (Refereed)
    Abstract [en]

    Positron emission tomography (PET) has evolved as a new diagnostic modality in cancer patients. Thioureylenes, such as thiouracil and methimazole, are known to be incorporated into growing melanin and selectively retained in melanotic melanoma. In the present study we used [(76)Br]5-bromo-2-thiouracil as tracer for PET imaging of human and murine melanotic melanoma transplanted subcutaneously into rats. The melanomas were clearly depicted 1 day after the injection, when [(76)Br]5-bromo-2-thiouracil was retained in the tumors though the overall radioactivity concentration in the body had declined. Accumulation of (76)Br was also seen in bladder, liver, and kidney. In addition, the rats were simultaneously injected with [(125)I]5-iodo-2-thiouracil and the tissue distribution of radioactivity was mapped by whole-body autoradiography. The results confirmed the selective uptake of thiouracil in the melanoma where the concentration of (125)I-radioactivity was about three-fold higher than that in the liver and lungs. These results show the possibility of using [(76)Br]5-bromo-2-thiouracil for PET diagnostics of melanoma, including dosimetry, prior to targeted therapy using [(131)I]5-iodo-2-thiouracil or [(211)At]5-astato-2-thiouracil.

  • 108.
    Nettelbladt, Otto S
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Respiratory Medicine and Allergology.
    Sundin, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Valind, Sven O
    Gustafsson, Gunnar R
    Lamberg, Kristina
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Respiratory Medicine and Allergology.
    Långström, Bengt
    Björnsson, Eythor H
    Combined fluorine-18-FDG and carbon-11-methionine PET for diagnosis of tumors in lung and mediastinum1998In: Journal of Nuclear Medicine, ISSN 0161-5505, E-ISSN 1535-5667, Vol. 39, no 4, p. 640-647Article in journal (Refereed)
    Abstract [en]

    We evaluated the value of PET using 18F-fluorodeoxyglucose (FDG) and 11C-methionine, individually or in combination, to distinguish malignant from benign tumors and to identify or exclude mediastinal metastases.

    METHODS:

    Seventeen patients with a tumor in the lung or mediastinum were evaluated with 18F-FDG and 11C-methionine PET. For morphological comparison, we used CT, and all findings were confirmed by histology of surgical resection specimens (n = 16) or by cytology (n = 1).

    RESULTS:

    All tumors were visualized equally well with both tracers, and there were no false-positive results. In 2 patients with a malignant tumor, coexisting pneumonia was correctly diagnosed as an inflammatory lesion because of its wedge-like shape. PET correctly excluded hilar invasion and mediastinal lymph node metastases in 10 of 14 patients with primary lung tumor. PET identified mediastinal metastases in 4 of 4 patients. CT failed to detect mediastinal tumor spread in 2 patients and gave a false-positive reading in 2 others. Significantly higher uptake (SUV) and transport rate (slope) values were obtained from malignant than benign lesions with both tracers. No major differences were seen in either the levels of significance or accuracy when the two tracers were compared. Slope values did not add further information to what was obtained with SUV. Density correction of SUV and slope values, to avoid the influence of surrounding air as well as tumor heterogeneity, increased these differences somewhat. Both tracers distinguished malignant from benign lesions with a 93% sensitivity and an accuracy of 89%-95%, but sensitivity improved to 100% when values from both tracers were combined.

    CONCLUSION:

    Fluorine-18-FDG and 11C-methionine PET visualized all tumors equally well and detected mediastinal spread better than CT. For differentiation purposes, the problems of false-positive and false-negative PET findings could not be safely overcome in a limited number of cases either by the use of both tracers, by the additional use of slope values or by lesion density correction.

  • 109. Nikolaou, A.
    et al.
    Thomas, D.
    Kampanellou, C.
    Alexandraki, K.
    Andersson, Lars-Göran
    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.
    Kaltsas, G.
    The value of C-11-5-hydroxy-tryptophan positron emission tomography in neuroendocrine tumor diagnosis and management: experience from one center2010In: Journal of Endocrinological Investigation, ISSN 0391-4097, E-ISSN 1720-8386, Vol. 33, no 11, p. 794-799Article in journal (Refereed)
    Abstract [en]

    Many neuroendocrine tumors (NET) are small and may escape localization by conventional imaging techniques. In such cases, C-11-5-hydroxy-tryptophan (C-11-5-HTP) positron emission tomography (PET) has been tested as an additional diagnostic tool. Nine patients with clinically, biochemically and/or histologically confirmed NET and negative computerized tomography (CT) or magnetic resonance imaging (MRI), and In-111-pentetreotide (Octreoscan) scintigraphy underwent imaging with C-11-5-HTP-PET/CT in order to: 1) detect the primary tumor lesion in three patients; 2) detect residual disease in two patients with appendiceal carcinoid, one with rectal carcinoid, one with midgut carcinoid, and one with ectopic ACTH secretion (EAS) due to residual pulmonary carcinoid; and 3) restage a patient with medullary thyroid carcinoma (MTC) and hepatic metastases. C-11-54HTP-PET/CT detected lesions in the mediastinum in a patient with EAS due to a pulmonary carcinoid, further hepatic metastases in a patient with carcinoid syndrome (CS) from a NET of unknown primary, further hepatic metastases in the patient with MTC, and hepatic metastases in the patient with midgut carcinoid. The C-11-5-HTP-PET/CT findings contributed to radical cure of the patient with recurrent EAS, and pointed towards bilateral adrenalectomy in the patient with EAS without evident primary tumor. In addition, C-11-5HTP-PET/CT directed towards combined surgical and medical treatment in the patient with CS and multiple rather than single hepatic metastases and in the patient with midgut carcinoid, and towards continuation of medical treatment in the patient with MTC. C-11-5-HTP-PET/CT is a useful imaging technique, providing additional information for the diagnosis, staging and decision-making regarding management of patients with NET.

  • 110.
    Nilsson, Dag
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurology.
    Lennernäs, Hans
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmacy.
    Fasth, Karl Johan
    Sundin, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Tedroff, Joakim
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurology.
    Aquilonius, Sten-Magnus
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurology.
    Hartvig, Per
    Långström, Bengt
    Absorption of L-DOPA from the proximal small intestine studied in the rhesus monkey by positron emission tomography1999In: European Journal of Pharmaceutical Sciences, ISSN 0928-0987, E-ISSN 1879-0720, Vol. 7, no 3, p. 185-189Article in journal (Refereed)
    Abstract [en]

    Positron emission tomography (PET) seems to be a valuable method for the understanding of intestinal absorption mechanisms, for simultaneous quantitation of absorption rate and distribution kinetics to the tissues of interest after oral drug delivery. PET was evaluated in three Rhesus monkeys for quantitation of the absorption rate from the gastrointestinal tract and the distribution kinetics into different organs. To obtain optimal standardized conditions for the measurement of absorption the drug was administered via a naso-duodenal catheter directly to the absorption site in the proximal small intestine. l-DOPA was used as study drug given in a suspension together with carbidopa and the radiomarker l-[beta-11C]DOPA. The l-DOPA suspension was given into the duodenum without and after administration of a suspension of six l-amino acids (120 mM) in order to investigate any interaction on the intestinal absorption and distribution of l-DOPA into the liver and brain tissue. Intestinal absorption was in general minor during the first study period and higher together with administered l-amino acids. The somewhat contradictory result with increased absorption when amino acids were present in the intestinal lumen, may be a consequence of increased intestinal motility initiated by the nutrient load.

  • 111. Nilsson, Inga-Lena
    et al.
    Arnberg, Fabian
    Zedenius, Jan
    Sundin, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology. Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden .
    Thyroid incidentaloma detected by fluorodeoxyglucose positron emission tomography/computed tomography: practical management algorithm2011In: World Journal of Surgery, ISSN 0364-2313, E-ISSN 1432-2323, Vol. 35, no 12, p. 2691-2697Article in journal (Refereed)
    Abstract [en]

    Background

    Our aim was to design a practical algorithm for management of an increasing number of incidental findings of thyroid lesions identified by 18F-fluorodeoxyglucose positron emission tomography with computed tomography (FDG-PET/CT).

    Methods

    The reports of 3641 patients examined by FDG-PET/CT for evaluation of nonthyroid cancer were reviewed. The anatomic locations and standardized uptake values (SUV) of any focally increased thyroid FDG uptake were reanalyzed and related to surrounding normal thyroid (TSUVmax/thySUVmean ratio) and liver (TSUVmax/liverSUVmean).

    Results

    Focal FDG uptakes in the thyroid were reported in 37 cases (1%; 26 women). Neoplastic thyroid lesions were diagnosed in 16 patients: papillary thyroid cancer in 9, follicular neoplasia in 5, and metastatic lesions (lung cancer and squamous cell carcinoma) in 2. Benign lesions were diagnosed in 11 patients. Ten patients with malignancy elsewhere did not undergo thyroid examination. In all, 11 patients underwent thyroid surgery (8 with papillary cancer, 3 with follicular adenoma); the median tumor size was 12 mm (8–40 mm). The TSUVmax/thySUVmean ratio was higher for the malignant lesions [median 5.53 (2.75–30.81) vs. 3.70 (1.82–31.70); P < 0.05], albeit with a considerable overlap between individual patients. The TSUVmax and TSUVmax/liverSUVmean did not differ between groups. The TSUVmax/thySUVmean and / thySUVmean ratios correlated with the tumor size (r = 0.64 and r = 0.66; P < 0.05).

    Conclusions

    An incidental finding of focal uptake of FDG in the thyroid is associated with a significant risk of thyroid cancer. If the patient would benefit from thyroidectomy if a malignancy were identified, further diagnostic workup with ultrasonography-guided fine-needle aspiration and cytology is recommended.

  • 112.
    Norlén, Olov
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Endocrine Surgery.
    Montan, Harald
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Hellman, Per
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Endocrine Surgery.
    Stålberg, Peter
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Endocrine Surgery.
    Sundin, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Preoperative Ga-68-DOTA-Somatostatin Analog-PET/CT Hybrid Imaging Increases Detection Rate of Intra-abdominal Small Intestinal Neuroendocrine Tumor Lesions2018In: World Journal of Surgery, ISSN 0364-2313, E-ISSN 1432-2323, Vol. 42, no 2, p. 498-505Article in journal (Refereed)
    Abstract [en]

    BACKGROUND:

    Small intestinal neuroendocrine tumors (SI-NETs) are the most common form of neoplasm in the small bowel. Radiological identification of primary tumors (PT), which may be multiple, is difficult, and therefore palpation of the entire small bowel is routinely performed during laparotomy. The aim was to determine detection rates of PT and peritoneal carcinomatosis (PC) with 68Ga-DOTATOC/TATE-PET/CT in comparison with i.v. contrast-enhanced computed tomography (CE-CT) and thus to clarify whether modern functional imaging can mitigate the need for palpation of bowel during surgery enabling oncologically adequate laparoscopic resection.

    METHODS:

    A total of 28 patients with SI-NET who preoperatively underwent both 68Ga-DOTATOC/TATE-PET/CT and CE-CT were included. The detection rates of PT and PC for PET/CT and CE-CT were compared to the findings in the surgical and histopathological reports. Appropriate statistical tests were used, and significance was set to p < 0.05.

    RESULTS:

    Out of 82 PT, 43 PT were not detected by any imaging modality. More PT lesions were detected with PET/CT (n = 39 [47.5%]) than with CE-CT (n = 10 [12.2%], p < 0.001). Also, PET/CT identified significantly more PC lesions than CE-CT (78 and 38%, p = 0.004, respectively).

    CONCLUSION:

    PET/CT detected more PT and PC lesions than CE-CT. Some PTs and PC lesions were only detected by one of the modalities, and CT performed in conjunction with PET/CT should therefore be performed as a fully diagnostic CE-CT for optimal results. Palpation of the small bowel remains crucial during surgery in these patients because several PTs escaped detection by both PET/CT and CE-CT.

  • 113.
    Norlén, Olov
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Endocrine Surgery.
    Nilsson, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Krause, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Stålberg, Peter
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Endocrine Surgery.
    Hellman, Per
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Endocrine Surgery.
    Sundin, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    11C-5-hydroxytryptophan positron emission tomography after radiofrequency ablation of neuroendocrine tumor liver metastases2012In: Nuclear Medicine and Biology, ISSN 0969-8051, E-ISSN 1872-9614, Vol. 39, no 6, p. 883-890Article in journal (Refereed)
    Abstract [en]

    Aim: The aim was to assess the feasibility of C-11-5-hydroxy-tryptophan positron emission tomography ( C-11-5-HTP-PET) in the follow-up after radiofrequency ablation (RFA) of liver metastases from neuroendocrine tumors (NETS). Background: Contrast-enhanced computed tomography (CECT) and contrast-enhanced ultrasound (CEUS) are commonly used to evaluate the liver after RFA of NETs. In general, C-11-5-HTP-PET is more sensitive in the visualization of NETs, but no studies have investigated its role after RFA.

    Methods: Six consecutive patients with liver metastases from NETs were subjected to RFA treatment. All patients underwent baseline imaging before RFA and on two occasions (1-2 and 6-11 months) after RFA. The imaging consisted of C-11-5-HTP-PET, CEUS and CECT on all three occasions.

    Results: Thirty RFA areas were evaluated, and residual tumors (RTs) were depicted in eight areas (22%). C-11-5-HTP-PET depicted RTs after RFA with maximum sensitivity (100%) and specificity (100%), using radiological follow-up as the gold standard. C-11-5-HTP-PET detected five out of eight RTs earlier than CECT or CEUS. In general, the sensitivity of C-11-5-HTP-PET exceeded that of CECT and CEUS for early visualization of NET liver metastases.

    Conclusion: C-11-5-HTP-PET can be used in the follow-up after RFA for the purpose of detecting RT, and it provides additional information to CEUS and CECT by detecting new lesions.

  • 114.
    Orlova, Anna
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology.
    Höglund, Johanna
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology.
    Lubberink, Mark
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology.
    Lebeda, Ondrej
    Gedda, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology.
    Lundqvist, Hans
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology.
    Tolmachev, Vladimir
    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.
    Comparative biodistribution of the radiohalogenated (Br, I and At) antibody A33: Implications for in vivo dosimetry2002In: Cancer Biotherapy and Radiopharmaceuticals, ISSN 1084-9785, E-ISSN 1557-8852, Vol. 17, no 4, p. 385-96Article in journal (Refereed)
    Abstract [en]

    The alpha-emitter astatine-211 (T(1/2) = 7.2 h) has great potential for use in targeted radionuclide therapy. Its potent alpha-radiation makes (211)At unsuitable for dose planning. Its x-rays can be used for gamma-camera monitoring of the radioactivity distribution during therapy but not for accurate estimation of absorbed dose in critical organs. This study was intended to establish whether the absorbed dose delivered by astatinated antibody could be accurately determined by analogue labeling with radiohalogens, better suited for quantitative measurements in vivo. PET facilitates quantitative pharmacokinetics; possible halogen labels are, e.g., (76)Br (T(1/2) = 16.2 h) and (124)I (T(1/2) = 4.18 d). Antibody A33 was labeled with (76)Br, (125)I and (211)At using N-succinimidyl-p-halobenzoates. The conjugates were co-injected into Sprague-Dawley rats. Radioactivity concentrations in different organs and tissues were measured at three time points. Pharmacokinetic data were used to calculate absorbed doses. (125)I and (76)Br reflected the biokinetics of astatine reasonably well. The absorbed doses in bladder, kidney, pancreas, liver, bone and brain were determined with 10% accuracy. The absorbed doses in stomach, spleen and thyroid were underestimated by a factor 2-3. Positron-emitting analogues can be used to predict the astatine-derived dose in critical organs. Correction factors should be used for stomach, spleen and thyroid.

  • 115. Plöckinger, Ursula
    et al.
    Couvelard, Anne
    Falconi, Massimo
    Sundin, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology, Radiology.
    Salazar, Ramon
    Christ, Emanuel
    de Herder, Wouter W.
    Gross, David
    Knapp, Wolfram H.
    Knigge, Ulrich P.
    Kulke, Matthew H.
    Pape, Ulrich F.
    Consensus guidelines for the management of patients with digestive neuroendocrine tumours: well-differentiated tumour/carcinoma of the appendix and goblet cell carcinoma2008In: Neuroendocrinology, ISSN 0028-3835, E-ISSN 1423-0194, Vol. 87, no 1, p. 20-30Article in journal (Refereed)
  • 116.
    Radecka, Eva
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Brekkan, Einar
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Urology.
    Juhlin, Claes
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences.
    Nilsson, L
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Thoracic Surgery.
    Sundin, Anders
    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.
    An unusual case of tumor thrombus in the inferior vena cava: A case report2003In: Acta Radiologica, ISSN 0284-1851, E-ISSN 1600-0455, Vol. 44, no 2, p. 160-161Article in journal (Refereed)
    Abstract [en]

    Adrenal cortical carcinoma (ACC) is a rare malignancy. Patients present either with a functional tumor or secondary to mass effect. In non-functioning tumors, the tumor size often exceeds 5 cm by the time of diagnosis, and tumor thrombus can occur. We report on a case of a small non-functioning ACC causing a large tumor thrombus in the inferior vena cava.

  • 117.
    Ramage, J. K.
    et al.
    Hampshire Hosp NHS Trust, Dept Gastroenterol, Basingstoke, Hants, England..
    De Herder, W. W.
    Erasmus MC, Div Endocrinol, Dept Internal Med, Rotterdam, Netherlands..
    Delle Fave, G.
    Osped St Andrea, Dept Digest & Liver Dis, Rome, Italy..
    Ferolla, P.
    Univ Perugia, Umbria Reg Canc Network, NET Ctr, I-06100 Perugia, Italy..
    Ferone, D.
    Univ Genoa, Dept Endocrine & Metab Sci DIMI, Genoa, Italy..
    Ito, T.
    Kyushu Univ Hosp, Pancreat Dis Branch, Fukuoka 812, Japan..
    Ruszniewski, P.
    Beaujon Hosp, Dept Gastroenterol, Clichy, France..
    Sundin, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    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..
    Taal, B.
    Netherlands Canc Ctr, Lijnden, Netherlands..
    Pascher, A.
    Charite, Dept Visceral & Transplant Surg, Campus Virchow Klinikum, D-13353 Berlin, Germany..
    ENETS Consensus Guidelines Update for Colorectal Neuroendocrine Neoplasms2016In: Neuroendocrinology, ISSN 0028-3835, E-ISSN 1423-0194, Vol. 103, no 2, p. 139-143Article in journal (Refereed)
  • 118.
    Ramage, John K
    et al.
    Kings Coll Hosp London, Hampshire Hosp NHS Trust, ENETS Ctr Excellence, Dept Gastroenterol, Basingstoke, Hants, England.
    Valle, Juan
    Univ Manchester, Christie ENETS Ctr Excellence, Dept Med Oncol, Manchester, Lancs, England.
    Nieveen van Dijkum, Els J M
    Dept Surg, Amsterdam, Netherlands.
    Sundin, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology. ENETS centre of excellence, Uppsala University Hopsital, Uppsala, Sweden.
    Pascher, Andreas
    Charite Univ Med Berlin, Dept Surg, Berlin, Germany; Univ Munster, Dept Visceral & Transplant Surg, Munster, Germany.
    Couvelard, Anne
    Hop Xavier Bichat, AP HP, Dept Pathol, Paris, France; Univ Paris Diderot, Paris, France.
    Kloeppel, Guenter
    Tech Univ Munich, Dept Pathol, Munich, 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.
    Colorectal Neuroendocrine Neoplasms - areas of unmet need2019In: Neuroendocrinology, ISSN 0028-3835, E-ISSN 1423-0194, Vol. 108, no 1, p. 45-53Article in journal (Refereed)
    Abstract [en]

    The subject of colorectal neuroendocrine neoplasms (NENs), subdivided into well-differentiated NENs, termed neuroendocrine tumours (NETs; grade (G) 1 and 2), and poorly differentiated NENs, termed neuroendocrine carcinomas (NECs; G3) according to the 2010 World Health Organisation (WHO) classification, has arguably not had as much attention or study as NENs occurring in other sites. Colorectal NETs and NECs are however easier to study than many others since they are usually not difficult to remove and are increasingly detected because of intensified colorectal cancer screening and surveillance programmes. Colorectal NETs and NECs show site-specific heterogeneity with variable behaviour and different therapeutic options; these various aspects provide unique challenges. Because of bowel cancer screening programmes, colorectal NENs, like conventional adenocarcinomas, may be diagnosed at a stage that is associated with improved survival. In this article we intend to describe and define areas of unmet needs relating to the epidemiology, classification, pathology, diagnosis and therapy of colorectal NETs (including NETs G3), colorectal NECs, and finally, mixed adeno-neuroendocrine carcinomas (MANECs) by reviewing and discussing the relevant literature.

  • 119.
    Razifar, Pasha
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Mathematics and Computer Science, Centre for Image Analysis. Uppsala University, Disciplinary Domain of Science and Technology, Mathematics and Computer Science, Department of Information Technology, Computerized Image Analysis.
    Hennings, Joakim
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Endocrine Surgery.
    Monazzam, Azita
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology, Oncology.
    Hellman, Per
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Endocrine Surgery.
    Långström, Bengt
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Biochemistry and Organic Chemistry.
    Sundin, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology, Radiology.
    Masked volume wise Principal Component Analysis of small adrenocortical tumours in dynamic [11C]-metomidate Positron Emission Tomography2009In: BMC Medical Imaging, ISSN 1471-2342, E-ISSN 1471-2342, Vol. 9:6Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: In previous clinical Positron Emission Tomography (PET) studies novel approaches for application of Principal Component Analysis (PCA) on dynamic PET images such as Masked Volume Wise PCA (MVW-PCA) have been introduced. MVW-PCA was shown to be a feasible multivariate analysis technique, which, without modeling assumptions, could extract and separate organs and tissues with different kinetic behaviors into different principal components (MVW-PCs) and improve the image quality. METHODS: In this study, MVW-PCA was applied to 14 dynamic 11C-metomidate-PET (MTO-PET) examinations of 7 patients with small adrenocortical tumours. MTO-PET was performed before and 3 days after starting per oral cortisone treatment. The whole dataset, reconstructed by filtered back projection (FBP) 0-45 minutes after the tracer injection, was used to study the tracer pharmacokinetics. RESULTS: Early, intermediate and late pharmacokinetic phases could be isolated in this manner. The MVW-PC1 images correlated well to the conventionally summed image data (15-45 minutes) but the image noise in the former was considerably lower. PET measurements performed by defining "hot spot" regions of interest (ROIs) comprising 4 contiguous pixels with the highest radioactivity concentration showed a trend towards higher SUVs when the ROIs were outlined in the MVW-PC1 component than in the summed images. Time activity curves derived from "50% cut-off" ROIs based on an isocontour function whereby the pixels with SUVs between 50 to 100% of the highest radioactivity concentration were delineated, showed a significant decrease of the SUVs in normal adrenal glands and in adrenocortical adenomas after cortisone treatment. CONCLUSION: In addition to the clear decrease in image noise and the improved contrast between different structures with MVW-PCA, the results indicate that the definition of ROIs may be more accurate and precise in MVW-PC1 images than in conventional summed images. This might improve the precision of PET measurements, for instance in therapy monitoring as well as for delineation of the tumour in radiation therapy planning.

  • 120.
    Sanchez-Crespo, Alejandro
    et al.
    Karolinska Univ Hosp, Dept Hosp Phys, Nucl Med, Stockholm, Sweden.; Karolinska Univ Hosp, Nukl Med A3 01, S-17176 Stockholm, Sweden..
    Christiansson, Frederik
    Nykopings Hosp, Dept Radiol, Nykoping, Sweden..
    Thur, Charlotte Karlsson
    Karolinska Inst, Dept Mol Med & Surg, Stockholm, Sweden..
    Lundblad, Henrik
    Karolinska Inst, Dept Mol Med & Surg, Stockholm, Sweden..
    Sundin, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Predictive value of [(18)F]-fluoride PET for monitoring bone remodeling in patients with orthopedic conditions treated with a Taylor spatial frame2017In: European Journal of Nuclear Medicine and Molecular Imaging, ISSN 1619-7070, E-ISSN 1619-7089, Vol. 44, no 3, p. 441-448Article in journal (Refereed)
    Abstract [en]

    PURPOSE: The Taylor Spatial Frame (TSF) is used to correct orthopedic conditions such as correction osteotomies in delayed fracture healing and pseudarthrosis. Long-term TSF-treatments are common and may lead to complications. Current conventional radiological methods are often unsatisfactory for therapy monitoring. Hence, an imaging technique capable of quantifying bone healing progression would be advantageous.

    METHODS: A cohort of 24 patients with different orthopedic conditions, pseudarthrosis (n = 10), deformities subjected to correction osteotomy (n = 9), and fracture (n = 5) underwent dynamic [(18)F]-fluoride (Na(18)F) PET/CT at 8 weeks and 4 months, respectively, after application of a TSF. Parametric images, corresponding to the net transport rate of [(18)F]-fluoride from plasma to bone, K i were calculated. The ratio of the maximum K i at PET scan 2 and 1 ([Formula: see text]) as well as the ratio of the maximum Standard Uptake Value at PET scan 2 and 1 ([Formula: see text]) were calculated for each individual. Different treatment end-points were scored, and the overall treatment outcome score was compared with the osteoblastic activity progression as scored with [Formula: see text] or [Formula: see text].

    RESULTS: [Formula: see text] and [Formula: see text] were not correlated within each orthopedic group (p > 0.1 for all groups), nor for the pooled population (p = 0.12). The distribution of [Formula: see text] was found significantly different among the different orthopedic groups (p = 0.0046) -also for [Formula: see text] (p = 0.022). The positive and negative treatment predictive values for [Formula: see text] were 66.7 % and 77.8 %, respectively. Corresponding values for [Formula: see text] were 25 % and 33.3 % CONCLUSIONS: The [Formula: see text] obtained from dynamic [(18)F]-fluoride-PET imaging is a promising predictive factor to evaluate changes in bone healing in response to TSF treatment.

  • 121.
    Sandqvist, Patricia
    et al.
    Karolinska Univ Hosp, Dept Med Radiat Phys & Nucl Med, Stockholm, Sweden.; Karolinska Inst, Dept Mol Med & Surg, Stockholm, Sweden.
    Nilsson, Inga-Lena
    Karolinska Inst, Dept Mol Med & Surg, Stockholm, Sweden.; Karolinska Univ Hosp, Dept Endocrine Surg, Stockholm, Sweden.
    Grybäck, Per
    Karolinska Univ Hosp, Dept Med Radiat Phys & Nucl Med, Stockholm, Sweden.; Karolinska Inst, Dept Mol Med & Surg, Stockholm, Sweden.
    Sanchez-Crespo, Alejandro
    Karolinska Univ Hosp, Dept Med Radiat Phys & Nucl Med, Stockholm, Sweden.
    Sundin, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    SPECT/CT's Advantage for Preoperative Localization of Small Parathyroid Adenomas in Primary Hyperparathyroidism2017In: Clinical Nuclear Medicine, ISSN 0363-9762, E-ISSN 1536-0229, Vol. 42, no 2, p. 109-114Article in journal (Refereed)
    Abstract [en]

    PURPOSES: The aims of this study were to assess the performance of Tc-sestamibi SPECT/CT, with diagnostic CT quality, compared with SPECT alone for preoperative localization of parathyroid adenomas and to assess the influence of adenoma weight on the correct adenoma lateralization with SPECT/CT and with SPECT alone.

    METHODS: Two hundred forty-nine consecutive patients, biochemically diagnosed with primary hyperparathyroidism, were examined with a combined SPECT/CT scanner. Subsequently, 200 patients with confirmed histopathology and biochemical cure after parathyroidectomy were included in this study (16 with multiglandular disease). For each patient, the SPECT-alone data were analyzed first. Thereafter, the CT information was added, and a new evaluation was performed with the combined data. In addition, for each patient, the diagnostic confidence with each method was graded on a scale based on the presence of different image features. The preoperative diagnostic findings were then compared with the surgical and histopathologic reports.

    RESULTS: The distribution of adenoma weights showed a peak at 210 mg, with a median at 338 mg. The sensitivity and specificity (multiglandular disease included) for correct classification of adenomas were significantly higher for SPECT/CT, 83% and 96%, respectively, than for SPECT alone, 80% and 93% (P < 0.01). Below 210 mg, the differences between SPECT/CT and SPECT alone in accurate adenoma lateralization were more prominent. Sixty-seven percent of all adenomas were graded with the highest confidence score with SPECT/CT compared with 53% with SPECT.

    CONCLUSIONS: SPECT/CT yields fewer false-positive findings than SPECT alone. The advantage of SPECT/CT over SPECT alone was most apparent for correct lateralization of small adenomas (<210 mg).

  • 122.
    Sandström, Mattias
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Fröss-Baron, Katarzyna
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Endocrine Tumor Biology.
    Khan, Tanweera Shaheena
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Endocrine Tumor Biology.
    Granberg, Dan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Endocrin Oncology.
    Sundin, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Lubberink, Mark
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Absorbed doses based on a single measurement point versus three measurement points in 600 patients with neuroendocrine tumours receiving 177Lu-DOTATATE therapy2018In: European Journal of Nuclear Medicine and Molecular Imaging, ISSN 1619-7070, E-ISSN 1619-7089, Vol. 45, no Supplement 1, p. S31-S31Article in journal (Other academic)
  • 123.
    Sandström, Mattias
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology, Section of Medical Physics.
    Garske, Ulrike
    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.
    Sundin, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Lundqvist, Hans
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology.
    Individualized dosimetry in patients undergoing therapy with Lu-177-DOTA-D-Phe(1)-Tyr(3)-octreotate2010In: European Journal of Nuclear Medicine and Molecular Imaging, ISSN 1619-7070, E-ISSN 1619-7089, Vol. 37, no 2, p. 212-225Article in journal (Refereed)
    Abstract [en]

    In recent years, targeted radionuclide therapy with [Lu-177-DOTA(0), Tyr(3)]octreotate for neuroendocrine tumours has yielded promising results. This therapy may be further improved by using individualized dosimetry allowing optimization of the absorbed dose to the tumours and the normal organs. The aim of this study was to investigate the feasibility and reliability of individualized dosimetry based on SPECT in comparison to conventional planar imaging. Attenuation-corrected SPECT data were analysed both by using organ-based volumes of interest (VOIs) to obtain the total radioactivity in the organ, and by using small VOIs to measure the tissue radioactivity concentration. During the first treatment session in 24 patients, imaging was performed 1, 24, 96 and 168 h after [Lu-177-DOTA(0), Tyr(3)]octreotate infusion. Absorbed doses in non tumour-affected kidney, liver and spleen were calculated and compared for all three methods (planar imaging, SPECT organ VOIs, SPECT small VOIs). Planar and SPECT dosimetry were comparable in areas free of tumours, but due to overlap the planar dosimetry highly overestimated the absorbed dose in organs with tumours. Furthermore, SPECT dosimetry based on small VOIs proved to be more reliable than whole-organ dosimetry. We conclude that SPECT dosimetry based on small VOIs is feasible and more accurate than conventional planar dosimetry, and thus may contribute towards optimising targeted radionuclide therapy.

  • 124.
    Sandström, Mattias
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Garske, Ulrike
    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.
    Granberg, Dan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Endocrine Oncology.
    Sundin, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Freedman, Nanette
    Hadassah Hebrew Univ Med Ctr, Dept Med Biophys & Nucl Med, Jerusalem, Israel;Tel Aviv Sourasky Med Ctr, Inst Nucl Med, Dept Imaging, Tel Aviv, Israel.
    Kidney dosimetry during (177)Lu-DOTATATE therapy in patients with neuroendocrine tumors: aspects on calculation and tolerance2018In: Acta Oncologica, ISSN 0284-186X, E-ISSN 1651-226X, Vol. 57, no 4, p. 516-521Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Fractionated therapy with (177)Lu-DOTATATE has been reported to be an effective treatment for patients with metastasized neuroendocrine tumors. To optimize the treatment, absorbed doses to risk organs are calculated for the individual patient. For each organ, absorbed dose due to activity in the organ itself (self-dose) and that originating from other organs (cross-dose) are calculated from serial measurements to obtain the activity distribution following treatment. The main aim of the present work were to calculate the cross-dose contribution to the total absorbed kidney dose.

    METHODS: Five hundred patients with neuroendocrine tumors undergoing therapy with (177)Lu-DOTATATE were included. Scintigraphic planar whole body images and single photon emission computed tomography/computed tomography (SPECT/CT) over the abdomen were acquired at 1, 4 and 7 days after treatment. Kidney self-dose was calculated based on radioactivity distribution obtained from SPECT/CT. Cross-dose to kidneys was estimated using organ-based analysis of planar whole body images and cross-fire dose factors from Olinda/EXM 1.1.

    RESULTS: Cross-dose to kidneys in the majority of patients were less than 2% and almost all cross-doses were less than 10%. Cross-dose exceeded 10% only in rare cases of patients with high tumor burden and low absorbed doses to kidneys.

    CONCLUSIONS: The absorbed dose from (177)Lu-octreotate to solid organs due to cross-fire is generally low and can usually be neglected.

  • 125.
    Sandström, Mattias
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Section of Nuclear Medicine and PET.
    Garske-Roman, Ulrike
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Section of Nuclear Medicine and PET.
    Granberg, Dan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Endocrine Oncology.
    Eriksson, B.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Endocrine Oncology.
    Sundin, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Lundqvist, Hans
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Biomedical Radiation Sciences.
    Lubberink, Mark
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Section of Nuclear Medicine and PET.
    Biological effective doses in 300 patients undergoing therapy with Lu-177-octreotate2013In: European Journal of Nuclear Medicine and Molecular Imaging, ISSN 1619-7070, E-ISSN 1619-7089, Vol. 40, no Suppl. 2, p. S201-S201Article in journal (Other academic)
  • 126.
    Sandström, Mattias
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Garske-Roman, Ulrike
    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 Radiology, Oncology and Radiation Science, Section of Nuclear Medicine and PET.
    Sundin, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Lubberink, Mark
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Fractional contribution of extrapolations after 96 h in absorbed dose calculation to kidneys in 450 patients with neuroendocrine tumours receiving Lu-177-DOTATATE therapy2015In: European Journal of Nuclear Medicine and Molecular Imaging, ISSN 1619-7070, E-ISSN 1619-7089, Vol. 42, no S1, p. S7-S8Article in journal (Other academic)
  • 127.
    Sandström, Mattias
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Section of Medical Physics. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Section of Nuclear Medicine and PET.
    Garske-Román, Ulrike
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Section of Nuclear Medicine and PET.
    Granberg, Dan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Endocrine Oncology.
    Johansson, Silvia
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Oncology.
    Widström, Charles
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Section of Medical Physics.
    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.
    Lundqvist, Hans
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Biomedical Radiation Sciences.
    Lubberink, Mark
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Section of Nuclear Medicine and PET.
    Individualized dosimetry of kidney and bone marrow in patients undergoing 177Lu-DOTA-octreotate treatment2013In: Journal of Nuclear Medicine, ISSN 0161-5505, E-ISSN 1535-5667, Vol. 54, no 1, p. 33-41Article in journal (Refereed)
    Abstract [en]

    The organs at risk in radionuclide therapy with 177Lu-octreotate are the bone marrow and the kidneys. The primary aim of this study was to develop an individualized dosimetry protocol for the bone marrow. The secondary aim was to identify those patients, undergoing fractionated therapy with 7.4 GBq/cycle, who first reached an accumulated dose of either 2 Gy to the bone marrow or 23 Gy to the kidneys. Methods: Two hundred patients with metastatic neuroendocrine tumors with high somatostatin receptor expression were included. After the administration of 7.4 GBq of 177Lu-octreotate, blood samples were drawn 6 times within the first 24 h. In 50 patients, additional blood samples were obtained at 96 and 168 h. Moreover, urine was collected from 30 patients during the first 24 h. Planar whole-body and SPECT/CT images over the abdomen were acquired at 24, 96, and 168 h after the infusion. Calculation of the absorbed radiation dose to the bone marrow was based on blood and urinary activity curves combined with organ-based analysis of the whole-body images. The absorbed dose to the kidney was calculated from the pharmacokinetic data obtained from SPECT/CT. Results: For a single cycle of 7.4 GBq, the absorbed dose to the bone marrow and the kidney ranged from 0.05 to 0.4 Gy and from 2 to 10 Gy, respectively. In 197 of 200 patients, the kidneys accumulated an absorbed dose of 23 Gy before the bone marrow reached 2 Gy. Between 2 and 10 cycles of 177Lu-octreotate could be administered before the upper dose limit for the individual patient was reached. Conclusion: A method based on repeated whole-body imaging in combination with blood and urinary activity data over time was developed to determine the absorbed dose to the bone marrow. The dose-limiting organ was the kidney in 197 of 200 patients. In 50% of the patients, more than 4 cycles of 7.4 GBq of 177Lu-octreotate could be administered, whereas 20% of the subjects were treated with fewer than 4 cycles. Individualized absorbed dose calculation is essential to optimize the therapy.

  • 128.
    Sandström, Mattias
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Ilan, Ezgi
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Fröss-Baron, Katarzyna
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Garske, Ulrike
    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.
    Eriksson, Barbro
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Endocrin Oncology.
    Sundin, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Lubberink, Mark
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Gender-related differences in absorbed dose to risk organs in patients receiving Lu-177-Octreotate therapy2017In: European Journal of Nuclear Medicine and Molecular Imaging, ISSN 1619-7070, E-ISSN 1619-7089, Vol. 44, p. S158-S158Article in journal (Other academic)
  • 129.
    Sandström, Mattias
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology.
    Ilan, Ezgi
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Sundin, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Lubberink, Mark
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Image quality measurements with 177Lu on a GE Discovery 670 CZT2017In: Journal of Nuclear Medicine, ISSN 0161-5505, E-ISSN 1535-5667, Vol. 58, no S1, article id 763Article in journal (Other academic)
  • 130.
    Sandström, Mattias
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Ilan, Ezgi
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Sundin, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Lubberink, Mark
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Is there a gender difference of absorbed dose to the risk organs in patients receiving 177Lu-Octreotate therapy?2017In: Journal of Nuclear Medicine, ISSN 0161-5505, E-ISSN 1535-5667, Vol. 58, no S1, article id 248Article in journal (Other academic)
  • 131.
    Sandström, Mattias
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology. Uppsala Univ, Nucl Med & PET, Uppsala, Sweden.
    Sundin, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology. Uppsala Univ, Nucl Med & PET, Uppsala, Sweden.
    Lubberink, Mark
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology. Uppsala Univ, Nucl Med & PET, Uppsala, Sweden.
    Ljungberg, M.
    Lund Univ, Dept Med Radiat Phys, Lund, Sweden.
    Image contrast of 177Lu-filled spheres as measured with a GE Discovery 670 CZT SPECT/CT system2018In: European Journal of Nuclear Medicine and Molecular Imaging, ISSN 1619-7070, E-ISSN 1619-7089, Vol. 45, no Supplement 1, p. S728-S729Article in journal (Other academic)
  • 132.
    Sandström, Mattias
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Section of Nuclear Medicine and PET. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Section of Medical Physics.
    Velikyan, Irina
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Section of Nuclear Medicine and PET.
    Garske-Roman, Ulrike
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Section of Nuclear Medicine and PET.
    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.
    Eriksson, Barbro
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Endocrine Oncology.
    Granberg, Dan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Endocrine Oncology.
    Lundqvist, Hans
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Biomedical Radiation Sciences.
    Sundin, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Lubberink, Mark
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Section of Nuclear Medicine and PET. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Section of Medical Physics.
    Comparative Biodistribution and Radiation Dosimetry of Ga-68-DOTATOC and Ga-68-DOTATATE in Patients with Neuroendocrine Tumors2013In: Journal of Nuclear Medicine, ISSN 0161-5505, E-ISSN 1535-5667, Vol. 54, no 10, p. 1755-1759Article in journal (Refereed)
    Abstract [en]

    Ga-68-DOTATOC and Ga-68-DOTATATE are 2 radiolabeled somatostatin analogs for in vivo diagnosis of neuroendocrine tumors with PET. The aim of the present work was to measure their comparative biodistribution and radiation dosimetry. Methods: Ten patients diagnosed with neuroendocrine tumors were included. Each patient underwent a 45-min dynamic and 3 whole-body PET/CT scans at 1, 2, and 3 h after injection of each tracer on consecutive days. Absorbed doses were calculated using OLINDA/EXM 1.1. Results: Data from 9 patients could be included in the analysis. Of the major organs, the highest uptake at 1, 2, and 3 h after injection was observed in the spleen, followed by kidneys and liver. For both tracers, the highest absorbed organ doses were seen in the spleen and urinary bladder wall, followed by kidney, adrenals, and liver. The absorbed doses to the liver and gallbladder wall were slightly but significantly higher for Ga-68-DOTATATE. The total effective dose was 0.021 +/- 0.003 mSv/MBq for both tracers. Conclusion: The effective dose for a typical 100-MBq administration of Ga-68-DOTATATE and Ga-68-DOTATOC is 2.1 mSv for both tracers. Therefore, from a radiation dosimetry point of view, there is no preference for either tracer for PET/CT evaluation of somatostatin receptor-expressing tumors.

  • 133.
    Sangfelt, Per
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Gastroenterology/Hepatology.
    Sundin, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Wanders, Alkwin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Molecular and Morphological Pathology.
    Rasmussen, Ib
    Karlson, Britt-Marie
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Upper Abdominal Surgery.
    Bergquist, Annika
    Rorsman, Fredrik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Gastroenterology/Hepatology.
    Monitoring Dominant Strictures in Primary Sclerosing Cholangitis with Brush Cytology and FDG-PET2014In: Journal of Hepatology, ISSN 0168-8278, E-ISSN 1600-0641, Vol. 61, no 6, p. 1352-1357Article in journal (Refereed)
    Abstract [en]

    BACKGROUND/AIMS: Despite high risk of cholangiocellular adenocarcinoma (CCA) it is unclear how surveillance of patients with primary sclerosing cholangitis (PSC) should be performed.

    METHOD: We evaluated a follow-up algorithm of brush cytology and positron emission tomography/computed tomography with [18F]fluorodeoxyglucose ([18F]FDG-PET/CT), measured as the maximum standardized uptake values normalized to the liver background (SUVmax/liver) at 180 minutes, in PSC patients with dominant bile duct strictures.

    RESULTS: Brush cytology with high grade dysplasia (HGD) was detected in 12/70 patients (17%), yielding diagnostic sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of 56%, 89%, 75% and 88%, respectively. Preemptive liver transplantations due to repeated HGD before manifest CCA were performed in six patients. Receiver operating characteristic (ROC) analysis of [18F]FDG uptake showed that a SUVmax/liver quotient of 3.3 was able to discriminate between CCA and non-malignant disease with a sensitivity, specificity, PPV and NPV for CCA of 89%, 92%, 62%, 98%, respectively. A SUVmax/liver >3.3 detected CCA in 8/9 patients whereas a quotient < 2.4 excluded CCA. Combining brush cytology and quantitative [18F]FDG-PET/CT yielded a sensitivity for HGD and/or CCA of 100% and a specificity of 88%.

    CONCLUSION: Early detection of HGD before manifest CCA is feasible with repeated brush cytology and may allow for preemptive liver transplantation. [18F]FDG-PET/CT has a high sensitivity for manifest CCA and a negative scan indicates a non-malignant state of the disease. Brush cytology and [18F]FDG-PET/CT are complementary in monitoring and managing PSC patients with dominant strictures.

  • 134. Schelin, Sonny
    et al.
    Claezon, Anders
    Sundin, Anders
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology.
    Wagrell, Lennart
    Effects of intraprostatic and periprostatic injections of mepivacaine epinephrine on intraprostatic blood flow during transurethral microwave thermotherapy: correlation with [15O]H2O-PET.2004In: J Endourol, ISSN 0892-7790, Vol. 18, no 10, p. 965-70Article in journal (Refereed)
  • 135. Schumacher, Martin C
    et al.
    Radecka, Eva
    Hellström, Magnus
    Jacobsson, Hans
    Sundin, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology. Department of Radiology, Molecular Medicine & Surgery, Karolinska Institutet, Karolinska University Hospital, Stockholm , Sweden.
    [11C]Acetate positron emission tomography-computed tomography imaging of prostate cancer lymph-node metastases correlated with histopathological findings after extended lymphadenectomy2015In: Scandinavian journal of urology, ISSN 2168-1805, E-ISSN 2168-1813, Vol. 49, no 1, p. 35-42Article in journal (Refereed)
    Abstract [en]

    Objective

    The aim of this study was to determine the efficacy of combined [11C]acetate positron emission tomography and computed tomography ([11C]acetate-PET/CT) in regional lymph-node staging in patients with prostate cancer (PCa).

    Material and methods

    [11C]Acetate-PET/CT was performed in 19 PCa patients who subsequently underwent extended pelvic lymph-node dissection (ePLND). The [11C]acetate-PET/CT results were compared with the surgical and histopathological findings from 13 defined lymph-node regions.

    Results

    [11C]Acetate-PET/CT was true-positive for lymph-node metastases in nine patients, false-positive in three, false-negative in one patient and true-negative in six. The patient-by-patient-based sensitivity was 90% and the specificity 67%, the positive predictive value (PPV) was 75% and the negative predictive value (NPV) 86%. From a total of 114 nodal regions (mean 5.9 regions per patient), 484 lymph nodes (mean 25.5 nodes per patient) were removed and evaluated histopathologically. Forty-six lymph nodes from 24 out of 114 (21%) nodal regions were positive for PCa metastasis. The nodal-region-based sensitivity of [11C]acetate-PET/CT was 62%, specificity was 89%, PPV 62% and NPV 89%.

    Conclusion

    [11C]Acetate-PET/CT detects PCa lymph-node metastases with high patient-by-patient-based sensitivity but low specificity, and low nodal-region-based sensitivity but high specificity. Its limited ability to detect microscopic lymph-node involvement makes ePLND essential in all patients diagnosed with positive nodes on [11C]acetate-PET/CT.

  • 136. Skorpil, Mikael
    et al.
    Rolheiser, Tyler
    Robertson, Harold
    Sundin, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology. Department of Molecular Medicine and Surgery, Karolinska Institute, Stockholm, Sweden.
    Svenningsson, Per
    Diffusion tensor fiber tractography of the olfactory tract2011In: Magnetic Resonance Imaging, ISSN 0730-725X, E-ISSN 1873-5894, Vol. 29, no 2, p. 289-292Article in journal (Refereed)
    Abstract [en]

    Magnetic resonance diffusion tensor imaging with fiber tracking is used for 3-dimensional visualization of the nervous system. Peripheral nerves and all cranial nerves, except for the olfactory tract, have previously been visualized. The olfactory tracts are difficult to depict with diffusion-weighted imaging due to the high sensitivity to susceptibility artifacts at the base of the skull. Here we report an optimized single-shot diffusion-weighted echo planar imaging sequence that can visualize the olfactory tracts with fiber tracking. Five healthy individuals were examined, and the olfactory tracts could be fiber tracked with the diffusion-weighted sequence. For comparison and as a negative control, an anosmic patient was examined. No olfactory tracts were visualized on T2-weighted nor diffusion-weighted fiber tracking images. Measuring diffusion in the olfactory tracts promise to facilitate the identification of different hyposmic and anosmic conditions.

  • 137. Skorpil, Mikael
    et al.
    Söderlund, Veli
    Sundin, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology. Center for Molecular Medicine, Department of Neurology and Clinical Neuroscience, Karolinska Institute, Stockholm, Sweden.
    Svenningsson, Per
    MRI diffusion in Parkinson's disease: using the technique's inherent directional information to study the olfactory bulb and substantia nigra2012In: Journal of Parkinson's Disease, ISSN 1877-7171, E-ISSN 1877-718X, Vol. 2, no 2, p. 171-180Article in journal (Refereed)
    Abstract [en]

    Pathological studies have shown that Parkinson's disease (PD) at early stages affects the olfactory bulb (OB) followed by an involvement of substantia nigra (SN) and other brain regions. Emerging imaging methodologies detect alterations in certain brain regions of living PD patients, which may support proper diagnosis and monitor disease progression. Here we used a novel approach of diffusion tensor imaging (DTI), taking advantage of the technique's inherent diffusion directional information, for region of interest (ROI) placement and diffusion measurements in the OB and SN. 16 healthy individuals and 18 early-moderate patients with PD, supported by reduced ¹²³I-Ioflupane putaminal binding, were examined with two identical DTI series. Olfaction was assessed with the 40-item UPSIT and Parkinsonian severity with UPDRS and Hoehn&Yahr. DTI measurements showed reduced fractional anisotropy (FA) for SN in the PD group in both DTI series. In OBs there was reduced FA in the PD group in the first series, but not in the second. As OBs are located in an area susceptible to artifacts, the coefficient of variation between the two DTI series was higher than for other brain regions. The UPSIT scores were much lower in the PD group than in healthy individuals. In conclusion, we describe a novel approach for more objective ROI placement in DTI, which enabled us to detect altered diffusion in the SN and OBs in PD. These data provides further support that diffusion MRI can be of high clinical utility as a biomarker to facilitate diagnosis and follow disease progression in PD.

  • 138.
    Sorbye, Halfdan
    et al.
    Haukeland Hosp, Dept Oncol & Clin Sci, Bergen, Norway.
    Baudin, Eric
    Gustave Roussy, Endocrine Oncol, Villejuif, France.
    Borbath, Ivan
    Clin Univ St Luc, Hepato Gastroenterol Unit, Brussels, Belgium.
    Caplin, Martyn
    Royal Free Hosp, Neuroendocrine Tumour Unit, Ctr Gastroenterol, London, England.
    Chen, Jie
    Sun Yat Sen Univ, Dept Gastroenterol, Affiliated Hosp 1, Guangzhou, Guangdong, Peoples R China.
    Cwikla, Jaroslaw B
    Univ Warmia & Mazury, Fac Med Sci, Olsztyn, Poland.
    Frilling, Andrea
    Imperial Coll London, Dept Surg & Canc, London, England.
    Grossman, Ashley
    Royal Free Hosp, Neuroendocrine Tumour Unit, London, England.
    Kaltsas, Gregory
    Univ Athens, Athens, Greece.
    Scarpa, Aldo
    Univ & Hosp Trust Verona, ARC Net Ctr Appl Res Canc, Verona, Italy; Univ & Hosp Trust Verona, Dept Diagnost & Publ Hlth, Sect Pathol, Verona, Italy.
    Welin, Staffan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Endocrin Oncology.
    Garcia-Carbonero, Rocio
    Univ Complutense Madrid, Hosp Univ 12 Octubre, Oncol Dept, CIBERONC,CNIO, Madrid, Spain.
    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 Needs in High-Grade Gastroenteropancreatic Neuroendocrine Neoplasms (WHO G3)2019In: Neuroendocrinology, ISSN 0028-3835, E-ISSN 1423-0194, Vol. 108, no 1, p. 54-62Article in journal (Refereed)
    Abstract [en]

    Gastroenteropancreatic (GEP) neuroendocrine neoplasms (NEN) are classified based on morphology and graded based on their proliferation rate as either well-differentiated low-grade (G1 to G2) neuroendocrine tumors (NET) or poorly differentiated high-grade (G3) neuroendocrine carcinomas (NEC). Recently, a new subgroup of well-differentiated high-grade pancreatic tumors (NET G3) has been defined. The GEP NEN G3 group consisting of both NEC and NET G3 has recently been shown to be a quite heterogeneous patient group concerning prognosis and treatment benefit, depending on factors such as the primary tumor site, differentiation, proliferation rate, and molecular alterations. In this review we discuss the existing data on diagnostics, treatment, and biomarkers in this patient group, the unmet needs, and the future perspectives.

  • 139. Stenberg, Å M
    et al.
    Sundin, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Larsson, B S
    Läckgren, Göran
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Paediatric Surgery.
    Stenberg, Arne
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Paediatric Surgery.
    Lack of distant migration after injection of a 125iodine labeled dextranomer based implant into the rabbit bladder1997In: Journal of Urology, ISSN 0022-5347, E-ISSN 1527-3792, Vol. 158, no 5, p. 1937-1941Article in journal (Refereed)
    Abstract [en]

    PURPOSE:

    In recent years endoscopic treatment of stress incontinence and vesicoureteral reflux has been introduced. Reports of possible particle migration of the injected material to distant organs in humans and experimental animals have led to a search for biological nonmigration products. An implant found to have a good clinical effect in these conditions is dextranomer in hyaluronan. We performed this study in rabbits to investigate the possible migration of dextranomer particles.

    MATERIALS AND METHODS:

    125Iodine labeled dextranomer particles were injected into the submucosal space of rabbit bladders, and samples of blood and various tissues were examined for radioactivity at scheduled intervals during a 28-day period. Furthermore, whole body autoradiography was performed 1 day, and 1 and 4 weeks after injection.

    RESULTS:

    Radioactivity was found in blood samples and in all tissues but it remained at the background activity level except in the thyroid, where uptake representing free 125iodine was detected. In the bladder 41 and 45% of the injected dose remained within the bladder wall 1 day and 4 weeks, respectively, after injection. The remainder of the dose probably disappeared from the bladder wall by leakage into the urine shortly after deposition, as indicated by the finding of 10-fold higher urine radioactivity levels at day 1 than at day 28 after injection.

    CONCLUSIONS:

    No distant migration of dextranomer particles occurs after submucosal injection of such an implant in the rabbit bladder wall.

  • 140.
    Sundin, A
    et al.
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology.
    Eriksson, B
    Bergström, M
    Bjurling, P
    Lindner, K J
    Oberg, K
    Långström, B
    Demonstration of [11C] 5-hydroxy-L-tryptophan uptake and decarboxylation in carcinoid tumors by specific positioning labeling in positron emission tomography.2000In: Nucl Med Biol, ISSN 0969-8051, Vol. 27, no 1, p. 33-41Article in journal (Refereed)
  • 141.
    Sundin, A
    et al.
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology.
    Eriksson, B
    Bergström, M
    Bjurling, P
    Lindner, K-J
    Oberg, K
    Långström, B
    Teknisk-naturvetenskapliga vetenskapsområdet, Chemistry, Department of Biochemistry and Organic Chemistry.
    Demonstration of (11C) 5-hydroxy-L-tryptophan uptake and decarboxylation in carcinoid tumors by specific positioning labeling in positron emission tomography.2000In: Nucl. Med. Biol.Article in journal (Other scientific)
  • 142.
    Sundin, A
    et al.
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology.
    Sörrensen, J
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology.
    Örlefors, H
    Department of Medical Sciences.
    Eriksson, B
    Bergström,
    Fasth,
    Långström,
    Whole-Body PET with [11C]-5-Hydroxytryptophan for Localization of Neuroendocrine Tumors.1999In: Clin Positron Imaging, ISSN 1095-0397, Vol. 2, no 6, p. 338-Article in journal (Refereed)
  • 143.
    Sundin, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Adrenal Molecular Imaging2016In: Imaging in Endocrine Disorders / [ed] Buchfelder M. & Guaraldi F, Basel: Karger , 2016, Vol. 45, p. 70-79Chapter in book (Refereed)
    Abstract [en]

    The major workload in the field of adrenal imaging comprises patients with adrenal tumors incidentally depicted by imaging performed for other reasons than adrenal disease. These so-called 'incidentalomas' are generally managed by CT and MRI, and molecular imaging techniques are required only for a few patients. PET/CT with 18F-fluorodeoxyglucose (18F-FDG) is useful for establishing whether an adrenal metastasis is the only lesion, and therefore is available for surgical resection, or if the disease is disseminated. 18F-FDG PET/CT may be applied to differ benign from malignant incidentalomas and can be helpful in the imaging of pheochromocytoma and adrenocortical cancer (ACC). 11C-metomidate PET/CT can differentiate adrenocortical from nonadrenocortical tumors and a suspected ACC may be characterized and staged before surgery. 11C-metomidate PET/CT is currently also used to help diagnose Conn's adenomas in primary aldosteronism, but further development is needed. Scintigraphy with 123I/131I-metaiodobenzylguanidine (MIBG) remains the mainstay for molecular imaging of pheochromocytoma and is mandatory in patients for whom 131I-MIBG therapy is considered. A PET tracer for the imaging of pheochromocytoma is the norepinephrine analogue (11)C-hydroxyephedrine that can be used to characterize equivocal lesions and for the follow-up and diagnosis of recurrent malignant disease. Other specialized PET tracers for the imaging of pheochromocytoma are 18F-fluorodihydroxyphenylalanine (18F-DOPA) and 18F-fluorodopamine.

  • 144.
    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.
    Imaging of adrenal masses with emphasis on adrenocortical tumors2012In: Theranostics, ISSN 1838-7640, E-ISSN 1838-7640, Vol. 2, no 5, p. 516-522Article in journal (Refereed)
    Abstract [en]

    Because of the more widespread and frequent use of cross-sectional techniques, mainly computed tomography (CT), an increasing number of adrenal tumors are detected as incidental findings (“incidentalomas”). These incidentaloma patients are much more frequent than those undergoing imaging because of symptoms related to adrenal disease. CT and magnetic resonance imaging (MRI) are in most patients sufficient for characterization and follow-up of the incidentaloma. In a minor portion of patients, biochemical screening reveals a functional tumor and further diagnostic work-up and therapy need to be performed according to the type of hormonal overproduction. In oncological patients, especially when the morphological imaging criteria indicate an adrenal metastasis, biopsy of the lesion should be considered after pheochromocytoma is ruled out biochemically. In the minority of patients in whom CT and MRI fail to characterize the tumor and when time is of essence, functional imaging mainly by positron emission tomography (PET) is available using various tracers. The most used PET tracer, [18F]fluoro-deoxy-glucose (18FDG), is able to differentiate benign from malignant adrenal tumors in many patients. 11C-metomidate (11C-MTO) is a more specialized PET tracer that binds to the 11-beta-hydroxylase enzyme in the adrenal cortex and thus makes it possible to differ adrenal tumors (benign adrenocortical adenoma and adrenocortical cancer) from those of non-adrenocortical origin.

  • 145.
    Sundin, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology. Karolinska University Hospital, Department of Radiology, Stockholm, Sweden.
    Imaging of neuroendocrine tumors2012In: Expert Opinion in Medical Diagnostics, ISSN 1753-0059, E-ISSN 1753-0067, Vol. 6, no 5, p. 473-483Article in journal (Refereed)
    Abstract [en]

    INTRODUCTION:

    The imaging needs in the individual neuroendocrine tumor (NET) patient are very diverse and the choice of method, or combination of techniques, depends on the characteristics of the particular type of NET and its presentation.

    AREAS COVERED:

    The various morphological and functional imaging methods and important methodological aspects are described. The imaging requirements for the various NET subtypes are explained and typical NET image findings are described and illustrated.

    EXPERT OPINION:

    The choice of the optimum imaging techniques is not only a matter of sensitivity and specificity but must also be considered in the light of the local availability and expertise in the department. Familiarity with contrast-enhancement technique for computed tomography (CT) and magnetic resonance imaging (MRI) is important in the interpretation and understanding of the imaging results. MRI including diffusion weighted imaging (DWI) for oncological imaging has been reported to improve tumor visualization and reader confidence and is expected to similarly be beneficial for NET imaging. Positron emission tomography (PET) using 68Ga-labeled somatostatin analogs is in several aspects superior to somatostatin receptor scintigraphy using Octreoscan®. Molecular imaging problem-solving tools, when PET/CT using 68Ga-labeled somatostatin analogs fails, are PET/CT with 11C-5-HTP and 18F-DOPA.

  • 146.
    Sundin, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Novel Functional Imaging of Neuroendocrine Tumors2018In: Endocrinology and metabolism clinics of North America (Print), ISSN 0889-8529, E-ISSN 1558-4410, Vol. 47, no 3, p. 505-523, article id S0889-8529(18)30515-2Article in journal (Refereed)
    Abstract [en]

    Somatostatin receptor imaging constitutes an integral part in neuroendocrine tumor visualization and should, because of its vastly superior performance, use 68Ga-DOTA-somatostatin analogue-PET/computed tomography rather than scintigraphy; it is particularly valuable for detecting metastases to lymph nodes, bone, peritoneum, and liver, which may be missed by morphologic imaging. 18FDG-PET/computed tomography is better suited for G3 and high-G2 neuroendocrine tumors. 18FDG-PET/computed tomography provides prognostic information. Alternative available PET tracers are 18F-DOPA and 11C-5-hydroxytryptophan. To take full advantage of the technique PET/computed tomography should include diagnostic intravenous contrast-enhanced computed tomography. PET/MRI is currently mainly investigational.

  • 147.
    Sundin, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Radioimmunolocalization and quantification of liver metastases and subcutaneous tumours from a human colonic cancer xenografted in the nude rat1993In: Acta Radiologica, Supplement, ISSN 0365-5954, Vol. 382, p. 1-29Article in journal (Refereed)
    Abstract [en]

    The purpose of the present investigation was to improve the conditions for radioimmunolocalization (RIL) and radioimmunotherapy (RIT) of colonic cancer, using experimental models of the human disease. A tumour model was created in the nude rat by intraportal injection of a mechanically disintegrated cell preparation of the human colonic cancer cell-line LS 174 T, producing liver metastases in a dose-dependent fashion. A conventional subcutaneous (s.c.) tumour model was also employed, where LS 174 T cells were inoculated into a hindleg of nude rats. A technique was developed for quantification of liver metastases by means of contrast-enhanced CT, using an iodinated lipid emulsion. CT-quantification proved feasible post mortem and also in vivo, the latter enabling repeated therapy evaluation in the same animal. Post mortem quantification of hepatic metastases was also accomplished by computer-based area calculation (CBAC) on serial liver sections. The three evaluation procedures were in agreement for quantification of intermediate and extensive hepatic metastatic growth, but not for livers with small and few metastases. A similar CT evaluation technique, may also be possible for human application. Several pharmacokinetic aspects of RIL were evaluated, using the 125I-labelled anti-carcinoembryonic antigen (CEA) monoclonal antibody (MAb) preparations I-38S1, AEC 38 and II-16. MAb AEC 38 was produced by additional purification of I-38S1 by anion exchange chromatography. Most MAb I-38S1, AEC 38 and II-16 accumulated in the s.c. xenografts during the first 24 h, the maximum being reached on days 2-4, depending on the MAb preparation used. The patterns of uptake and clearance of AEC 38, I-38S1 and II-16, found in gamma camera registrations, were in agreement with those of external detector measurements. Additional purification of I-38S1 by anion exchange chromatography improved the in vivo MAb uptake in s.c. xenografts, but its immunoreactivity in vitro was impaired by this procedure. The uptake of I-38S1 in hepatic metastases was not size dependent and was higher than in s.c. xenografts, irrespective of the mode of MAb injection (i.p. or i.v.). Uptake of I-38S1 in s.c. xenografts was independent on injection mode. By contrast, in liver metastases there was a marked tendency toward a higher uptake of I-38S1 following i.p. vis-a-vis i.v. antibody administration, although not statistically significant, possibly due to an apparent variability between animals and between different liver metastases in the same rat. This variability was not evident for s.c. xenografts.

  • 148.
    Sundin, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology. Karolinska Institute and Karolinska University Hospital, Stockholm, Sweden.
    Radiological and nuclear medicine imaging of gastroenteropancreatic neuroendocrine tumours2012In: Baillière's Best Practice & Research: Clinical Gastroenterology, ISSN 1521-6918, E-ISSN 1532-1916, Vol. 26, no 6, p. 803-818Article in journal (Refereed)
    Abstract [en]

    Neuroendocrine tumours (NETs) comprise a heterogeneous group of neoplasms with very varying clinical expression. A functioning NET, for instance in the pancreas, may be very small and yet give rise to severe endocrine symptoms whereas a patient with a small bowel tumour may present with diffuse symptoms and disseminated disease with a palpable bulky liver. Imaging of NETs is therefore challenging and the imaging needs in the various patients are diverse. The basic modalities for NET imaging are computed tomography (CT) or magnetic resonance imaging (MRI) in combination with somatostatin receptor imaging (SMI) by scintigraphy with 111In-labelled octreotide (OctreoScan) or more recently by positron emission tomography (PET) with 68Ga-labelled somatostatin analogues. In this review these various morphological and functional imaging modalities and important methodological aspects are described. Imaging requirements for the various types of NETs are discussed and typical image findings are illustrated.

  • 149.
    Sundin, Anders
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Arnold, Rudolf
    Philipps Univ, Dept Gastroenterol & Endocrino.
    Baudin, Eric
    Gustave Roussy Canc Campus, Dept Endocrine Oncol & Nucl Med.
    Cwikla, Jaroslaw B
    Univ Warmia & Mazury, Fac Med Sci, Dept Radiol.
    Eriksson, Barbro
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Endocrine Tumor Biology.
    Fanti, Stefano
    Univ Bologna, Policlin S Orsola, Dept Nucl Med.
    Fazio, Nicola
    European Inst Oncol, Unit Gastrointestinal Med Oncol & Neuroendocrine.
    Giammarile, Francesco
    Univ Lyon, Hosp Civils Lyon, Nucl Med Dept.
    Hicks, Rodney J
    Peter MacCallum Canc Ctr, Canc Imaging.
    Kjaer, Andreas
    Rigshosp, Dept Clin Physiol Nucl Med & PET; Rigshosp, Cluster Mol Imaging; Univ Copenhagen.
    Krenning, Eric
    Erasmus MC, Dept Nucl Med.
    Kwekkeboom, Dik
    Erasmus MC, Dept Nucl Med.
    Lombard-Bohas, Catherine
    Hop Edouard Herriot, Hosp Civils Lyon, Inst Canc.
    O'Connor, Juan M
    Gastroenterol Hosp B Udaondo, Alexander Fleming Inst.
    O'Toole, Dermot
    Univ Dublin, St Jamess Hosp, Trinity Coll Dublin; St Vincents Univ Hosp.
    Rockall, Andrea
    Royal Marsden NHS Fdn Trust, Dept Radiol; Imperial Coll London.
    Wiedenmann, Bertram
    Charite Univ Med Berlin, Campus Charite Mitte, Dept Gastroenterol & Hepatol; Charite Univ Med Berlin, Campus Virchow Klinikum.
    Valle, Juan W
    Univ Manchester, Christie NHS Fdn Trust, Inst Canc Sci.
    Vullierme, Marie-Pierre
    Hop Beaujon, Serv Gastroenterol.
    ENETS Consensus Guidelines for the Standards of Care in Neuroendocrine Tumors: Radiological, Nuclear Medicine & Hybrid Imaging.2017In: Neuroendocrinology, ISSN 0028-3835, E-ISSN 1423-0194, Vol. 105, no 3, p. 212-244Article in journal (Refereed)
    Abstract [en]

    Contrast-enhanced computed tomography (CT) of the neckthorax-abdomen and pelvis, including 3-phase examination of the liver, constitutes the basic imaging for primary neuroendocrine tumor (NET) diagnosis, staging, surveillance, and therapy monitoring. CT characterization of lymph nodes is difficult because of inadequate size criteria (short axis diameter), and bone metastases are often missed. Contrast-enhanced magnetic resonance imaging (MRI) including diffusion-weighted imaging is preferred for the examination of the liver, pancreas, brain and bone. MRI may miss small lung metastases. MRI is less well suited than CT for the examination of extended body areas because of the longer examination procedure. Ultrasonography (US) frequently provides the initial diagnosis of liver metastases and contrast-enhanced US is excellent to characterize liver lesions that remain equivocal on CT/MRI. US is the method of choice to guide the biopsy needle for the histopathological NET diagnosis. US cannot visualize thoracic NET lesions for which CTguided biopsy therefore is used. Endocopic US is the most sensitive method to diagnose pancreatic NETs, and additionally allows for biopsy. Intraoperative US facilitates lesion detection in the pancreas and liver. Somatostatin receptor imaging should be a part of the tumor staging, preoperative imaging and restaging, for which 68 Ga-DOTA-somatostatin analog PET/CT is recommended, which is vastly superior to somatostatin receptor scintigraphy, and facilitates the diagnosis of most types of NET lesions, for example lymph node metastases, bone metastases, liver metastases, peritoneal lesions, and primary small intestinal NETs. (18)FDG-PET/CT is better suited for G3 and high G2 NETs, which generally have higher glucose metabolism and less somatostatin receptor expression than low-grade NETs, and additionally provides prognostic information.

  • 150.
    Sundin, Anders
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology, Radiology.
    Eriksson, Barbro
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Endocrine Oncology.
    Bergström, Mats
    Uppsala University Petcentre (Imanet).
    Långström, Bengt
    Uppsala University Petcentre (Imanet).
    Öberg, Kjell
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Endocrine Oncology.
    Örlefors, Håkan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Endocrine Oncology.
    PET in the diagnosis of neuroendocrine tumors2004In: Annals of the New York Academy of Sciences, ISSN 0077-8923, E-ISSN 1749-6632, Vol. 1014, p. 246-257Article in journal (Refereed)
    Abstract [en]

    For general oncological imaging, positron emission tomography (PET) using [18F]fluoro-deoxy-glucose (FDG) has evolved as a powerful functional imaging modality. Unfortunately, FDG-PET has not been as advantageous for imaging gastropancreatic neuroendocrine tumors, and only tumors with high proliferative activity and low differentiation have shown an increased FDG uptake. Therefore, the 11C-labeled amine precursors L-dihydroxyphenylalanine and 5-hydroxy-L-tryptophan (5-HTP) were developed for PET imaging of these tumors. Because of the higher tumor uptake of the latter tracer in a study of patients with endocrine pancreatic tumors, 11C-5-HTP was chosen for further evaluation. In comparative studies of patients with carcinoids and endocrine pancreatic tumors, 5-HTP-PET proved better than CT and somatostatin receptor scintigraphy for tumor visualization, and many small, previously overlooked lesions were diagnosed by 11C-5-HTP-PET. The strong correlation found during medical treatment between the changes in the transport rate constant at repeated PET and those of U-HIAA indicates the possible use of 11C-5-HTP-PET also for therapy monitoring. By premedication of patients with Carbidopa orally before PET examination, in order to block the aromatic amino acid decarboxylase enzyme, the decarboxylation rate of 11C-5-HTP was decreased, leading to a higher tumor uptake and a considerably lower urinary radioactivity concentration.

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