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Örlefors, Håkan
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Publikasjoner (10 av 13) Visa alla publikasjoner
Örlefors, H., Sundin, A., Eriksson, B., Skogseid, B., Öberg, K., Åkerström, G. & Hellman, P. (2012). PET-Guided Surgery: High Correlation between Positron Emission Tomography with 11C-5-Hydroxytryptophane (5-HTP) and Surgical Findings in Abdominal Neuroendocrine Tumours. Cancers, 4(1), 100-112
Åpne denne publikasjonen i ny fane eller vindu >>PET-Guided Surgery: High Correlation between Positron Emission Tomography with 11C-5-Hydroxytryptophane (5-HTP) and Surgical Findings in Abdominal Neuroendocrine Tumours
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2012 (engelsk)Inngår i: Cancers, ISSN 2072-6694, Vol. 4, nr 1, s. 100-112Artikkel i tidsskrift (Annet vitenskapelig) Published
Abstract [en]

Positron emission tomography (PET) with 11C-labeled 5-hydroxytryptophane (5-HTP) is a sensitive technique to visualize neuroendocrine tumours (NETs), due to high intracellular uptake of amine-precursors like L-dihydroxyphenylalanine (L-DOPA) and 5-HTP. NETs are often small and difficult to localize in spite of overt clinical symptoms due to hormonal excess. In our study, 38 consecutive NET patients underwent 11C-5-HTP-PET and morphological imaging by CT within 12 weeks prior to surgery. Surgical, histopathological and 5-HTP PET findings were correlated. 11C-5-HTP-PET corresponded to the surgical findings in 31 cases, was false negative in six, and true negative in one case resulting in 83.8% sensitivity and 100% specificity. Positive predicted value was 100%. In 11 patients 11C-5-HTP-PET was the only imaging method applied to localize the tumour. Thus, we could demonstrate that functional imaging by 11C-5-HTP-PET in many cases adds vital preoperative diagnostic information and in more than every fourth patient was the only imaging method that will guide the surgeon in finding the NET-lesion. Although the present results demonstrates that 11C-5-HTP may be used as an universal NET tracer, the sensitivity to visualize benign insulinomas and non functioning pancreatic NETs was lower.

Emneord
neuroendocrine tumour, positron emission tomography, hydroxytryptophane, insulinoma, surgery
HSV kategori
Identifikatorer
urn:nbn:se:uu:diva-192102 (URN)10.3390/cancers4010100 (DOI)
Tilgjengelig fra: 2013-01-16 Laget: 2013-01-16 Sist oppdatert: 2013-01-16bibliografisk kontrollert
Hellman, P., Linder, F., Hennings, J., Hessman, O., Eriksson, B., Örlefors, H. & Åkerström, G. (2006). Bilateral adrenalectomy for ectopic Cushing syndrome -: discussions on technique and indication. World J Surg, 30(5), 909-916
Åpne denne publikasjonen i ny fane eller vindu >>Bilateral adrenalectomy for ectopic Cushing syndrome -: discussions on technique and indication
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2006 (engelsk)Inngår i: World J Surg, Vol. 30, nr 5, s. 909-916Artikkel i tidsskrift (Fagfellevurdert) Published
Identifikatorer
urn:nbn:se:uu:diva-74397 (URN)16467980 (PubMedID)
Tilgjengelig fra: 2006-06-08 Laget: 2006-06-08 Sist oppdatert: 2011-01-11
Örlefors, H., Sundin, A., Lu, L., Öberg, K., Långström, B., Eriksson, B. & Bergström, M. (2006). Carbidopa pretreatment improves image interpretation and visualisation of carcinoid tumours with 11C-5-hydroxytryptophan positron emission tomography. European Journal of Nuclear Medicine and Molecular Imaging, 33(1), 60-65
Åpne denne publikasjonen i ny fane eller vindu >>Carbidopa pretreatment improves image interpretation and visualisation of carcinoid tumours with 11C-5-hydroxytryptophan positron emission tomography
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2006 (engelsk)Inngår i: European Journal of Nuclear Medicine and Molecular Imaging, ISSN 1619-7070, E-ISSN 1619-7089, Vol. 33, nr 1, s. 60-65Artikkel i tidsskrift (Fagfellevurdert) Published
Abstract [en]

PURPOSE: Positron emission tomography (PET) with 11C-5-hydroxytryptophan (5-HTP) as tracer is a promising imaging instrument in the management of patients with neuroendocrine tumours (NETs). However, high radioactivity concentrations in the urinary collecting system sometimes produce image reconstruction artefacts that can make detection of small NETs difficult. As a means to decrease urinary excretion of radioactivity and thereby improve image quality, we examined the effect of pretreatment with carbidopa (CD), a peripheral inhibitor of aromatic amino acid decarboxylase (AADC), which converts 5-HTP to serotonin (5-hydroxytryptamine, 5-HT). METHODS: Six patients with midgut carcinoid metastases were examined with 11C-5-HTP PET before and 1 h after oral administration of 100 or 200 mg of CD. RESULTS: There was a fourfold significant reduction of tracer uptake in the urinary collecting system after CD administration (p=0.0277, n=6), with a mean standard uptake value (SUV) of 155+/-195 before CD and 39+/-14 after CD. In tumour lesions there was a significant increase in SUV after CD administration (p<0. 0001, n=18), with a mean SUV of 11+/-3 before CD and 14+/-3 after CD. There was no difference between the doses (100 and 200 mg) of CD in this respect. In all patients, image interpretation and tumour detection were markedly improved after CD administration. CONCLUSION: We conclude that CD premedication improves 11C-5-HTP PET image quality and facilitates detection of NET lesions. Because of the similarity of metabolic pathways, this method could probably be applied to improve PET imaging using other tracers like 18F-DOPA and 11C-DOPA.

Emneord
5-Hydroxytryptophan/*diagnostic use, Carbidopa/*diagnostic use, Carbon Radioisotopes, Carcinoid Tumor/*radionuclide imaging/*secondary, Female, Humans, Image Enhancement/*methods, Liver Neoplasms/*radionuclide imaging/*secondary, Lymphatic Metastasis, Male, Positron-Emission Tomography/*methods, Radiopharmaceuticals/diagnostic use, Reproducibility of Results, Sensitivity and Specificity
HSV kategori
Identifikatorer
urn:nbn:se:uu:diva-16734 (URN)10.1007/s00259-005-1891-z (DOI)16184369 (PubMedID)
Tilgjengelig fra: 2008-06-03 Laget: 2008-06-03 Sist oppdatert: 2017-12-08bibliografisk kontrollert
Granberg, D., Skogseid, B., Welin, S., Örlefors, H., Öberg, K. & Wilander, E. (2006). Gastrin-releasing-peptide in neuroendorine tumours. Acta Oncologica, 45(1), 23-27
Åpne denne publikasjonen i ny fane eller vindu >>Gastrin-releasing-peptide in neuroendorine tumours
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2006 (engelsk)Inngår i: Acta Oncologica, ISSN 0284-186X, E-ISSN 1651-226X, Vol. 45, nr 1, s. 23-27Artikkel i tidsskrift (Fagfellevurdert) Published
Abstract [en]

In a substantial proportion of cases with endocrine malignant disease the primary lesion cannot be localised and the pathologist hesitates upon the origin of the tumour. Well differentiated neuroendocrine carcinomas of the small bowel can usually be identified by the strong serotonin immunoreactivity, but foregut carcinoids may also stain positive for serotonin and the differential diagnosis between the various foregut tumours may be difficult. We examined if immunostaining for gastrin-releasing-peptide (GRP) may aid in establishing the origin of an unknown neuroendocrine tumour. Tumour tissue from 79 patients (27 lung carcinoids, 4 thymic carcinoids, 4 gastric neuroendocrine tumours, 17 pancreatic well differentiated neuroendocrine carcinomas, 1 duodenal well differentiated neuroendocrine tumour and 26 well differentiated neuroendocrine carcinomas of the small bowel) were immunostained with antibodies against GRP and serotonin. Positive staining for GRP was found in 12/27 lung carcinoids. All other tumour types were consistently GRP-negative (p?<?0.0001). We conclude that immunostaining for GRP may aid in defining the origin of the tumour, and that GRP-immunoreactivity increases the suspicion of a lung carcinoid.

Emneord
Diagnosis; Differential, Female, Gastrins/*biosynthesis, Gastrointestinal Neoplasms/*secondary, Humans, Immunohistochemistry, Lung Neoplasms/*secondary, Middle Aged, Neoplasms; Unknown Primary/*diagnosis/metabolism, Neuroendocrine Tumors/metabolism/*pathology, Peptides/*metabolism, Prospective Studies, Thymus Neoplasms/*secondary
HSV kategori
Identifikatorer
urn:nbn:se:uu:diva-21379 (URN)10.1080/02841860500367434 (DOI)16464792 (PubMedID)
Tilgjengelig fra: 2007-02-24 Laget: 2007-02-24 Sist oppdatert: 2017-12-08bibliografisk kontrollert
Eriksson, B., Örlefors, H., Öberg, K., Sundin, A., Bergström, M. & Långström, B. (2005). Developments in PET for the detection of endocrine tumours. Baillière's Best Practice & Research. Clinical Endocrinology & Metabolism, 19(2), 311-324
Åpne denne publikasjonen i ny fane eller vindu >>Developments in PET for the detection of endocrine tumours
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2005 (engelsk)Inngår i: Baillière's Best Practice & Research. Clinical Endocrinology & Metabolism, ISSN 1521-690X, E-ISSN 1532-1908, Vol. 19, nr 2, s. 311-324Artikkel i tidsskrift (Annet vitenskapelig) Published
Abstract [en]

Positron emission tomography (PET) supplies a range of labelled compounds to be used for the characterization of tumour biochemistry. Some of these have proved to be of value for clinical diagnosis, treatment follow-up, and clinical research. 18F-fluorodeoxyglucose PET scanning is now a widely accepted imaging approach in clinical oncology, reflecting increased expression of glucose transporters in cancerous tissue. This tracer, however, does not show sufficient uptake in well-differentiated tumours such as neuroendocrine tumours. Endocrine tumours have the unique characteristics of taking up and decarboxylating amine precursors. These so-called APUD characteristics offer highly specific targets for PET tracers. Using this approach, radiopharmaceuticals such as [11C]-5-hydroxytryptophan and [11C]-l-dihydroxyphenylalanine for localization of carcinoid and endocrine pancreatic tumours, 6-[18F]-fluorodopamine and [11C]-hydroxyephedrine for phaeochromocytomas, and [11C]-metomidate for adrenal cortical tumours have been developed. Functional imaging with PET using these compounds is now being employed to complement rather than replace other imaging modalities. Development of new PET radiopharmaceuticals may in the future allow in vivo detection of tumour biological properties, such as malignant potential and responsiveness to treatment.

Emneord
Carbon Radioisotopes/diagnostic use, Endocrine Gland Neoplasms/*radionuclide imaging, Fluorine Radioisotopes/diagnostic use, Humans, Neuroendocrine Tumors/*radionuclide imaging, Positron-Emission Tomography/*methods, Radiopharmaceuticals/*diagnostic use
HSV kategori
Identifikatorer
urn:nbn:se:uu:diva-75481 (URN)10.1016/j.beem.2004.11.001 (DOI)15763703 (PubMedID)
Tilgjengelig fra: 2007-04-18 Laget: 2007-04-18 Sist oppdatert: 2017-12-14bibliografisk kontrollert
Örlefors, H., Sundin, A., Garske, U., Juhlin, C., Öberg, K., Skogseid, B., . . . Eriksson, B. (2005). Whole-Body 11C-5-Hydroxytryptophan Positron Emission Tomography as a Universal Imaging Technique for Neuroendocrine Tumors: Comparison with Somatostatin Receptor Scintigraphy and Computed Tomography. Journal of Clinical Endocrinology and Metabolism, 90(6), 3392-3400
Åpne denne publikasjonen i ny fane eller vindu >>Whole-Body 11C-5-Hydroxytryptophan Positron Emission Tomography as a Universal Imaging Technique for Neuroendocrine Tumors: Comparison with Somatostatin Receptor Scintigraphy and Computed Tomography
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2005 (engelsk)Inngår i: Journal of Clinical Endocrinology and Metabolism, ISSN 0021-972X, E-ISSN 1945-7197, Vol. 90, nr 6, s. 3392-3400Artikkel i tidsskrift (Fagfellevurdert) Published
HSV kategori
Identifikatorer
urn:nbn:se:uu:diva-73096 (URN)10.1210/jc.2004-1938 (DOI)15755858 (PubMedID)
Tilgjengelig fra: 2006-01-19 Laget: 2006-01-19 Sist oppdatert: 2017-12-14bibliografisk kontrollert
Sundin, A., Eriksson, B., Bergström, M., Långström, B., Öberg, K. & Örlefors, H. (2004). PET in the diagnosis of neuroendocrine tumors. Annals of the New York Academy of Sciences, 1014, 246-257
Åpne denne publikasjonen i ny fane eller vindu >>PET in the diagnosis of neuroendocrine tumors
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2004 (engelsk)Inngår i: Annals of the New York Academy of Sciences, ISSN 0077-8923, E-ISSN 1749-6632, Vol. 1014, s. 246-257Artikkel i tidsskrift (Fagfellevurdert) Published
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.

Emneord
Carcinoid Tumor/*radionuclide imaging, Humans, Neuroendocrine Tumors/*radionuclide imaging, Pancreatic Neoplasms/*radionuclide imaging, Tomography; Emission-Computed/*methods
HSV kategori
Identifikatorer
urn:nbn:se:uu:diva-73083 (URN)10.1196/annals.1294.027 (DOI)15153441 (PubMedID)
Tilgjengelig fra: 2005-09-20 Laget: 2005-09-20 Sist oppdatert: 2017-12-14bibliografisk kontrollert
Eriksson, B., Bergström, M., Örlefors, H., Sundin, A., Öberg, K. & Långström, B. (2003). PET for clinical diagnosis and research in neuroendocrine tumors. In: Diagn Nuclear Medicine 4th edition (pp. 747-754).
Åpne denne publikasjonen i ny fane eller vindu >>PET for clinical diagnosis and research in neuroendocrine tumors
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2003 (engelsk)Inngår i: Diagn Nuclear Medicine 4th edition, 2003, s. 747-754Kapittel i bok, del av antologi (Fagfellevurdert)
Identifikatorer
urn:nbn:se:uu:diva-23151 (URN)
Tilgjengelig fra: 2007-01-25 Laget: 2007-01-25
Eriksson, B., Bergström, M., Sundin, A., Juhlin, C., Örlefors, H., Öberg, K. & Långström, B. (2002). The role of PET in localization of neuroendocrine and adrenocortical tumors. Annals of the New York Academy of Sciences, 970, 159-169
Åpne denne publikasjonen i ny fane eller vindu >>The role of PET in localization of neuroendocrine and adrenocortical tumors
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2002 (engelsk)Inngår i: Annals of the New York Academy of Sciences, ISSN 0077-8923, E-ISSN 1749-6632, Vol. 970, s. 159-169Artikkel i tidsskrift (Fagfellevurdert) Published
Abstract [en]

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

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

Emneord
5-Hydroxytryptophan/metabolism, Adrenal Gland Neoplasms/metabolism/*radionuclide imaging/therapy, Carbon Radioisotopes/metabolism, Etomidate/*analogs & derivatives/metabolism, Fluorine Radioisotopes/metabolism, Humans, Levodopa/metabolism, Neuroendocrine Tumors/metabolism/*radionuclide imaging/therapy, Radioactive Tracers, Research Support; Non-U.S. Gov't, Tomography; Emission-Computed/*methods
HSV kategori
Identifikatorer
urn:nbn:se:uu:diva-73661 (URN)10.1111/j.1749-6632.2002.tb04422.x (DOI)12381551 (PubMedID)
Tilgjengelig fra: 2007-03-14 Laget: 2007-03-14 Sist oppdatert: 2017-12-14bibliografisk kontrollert
Eriksson, B., Bergström, M., Örlefors, H., Sundin, A., Öberg, K. & Långström, B. (2000). Use of PET in neuroendocrine tumors: In vivo applications and in vitro studies. The Quarterly journal of nuclear medicine, 44(1), 68-76
Åpne denne publikasjonen i ny fane eller vindu >>Use of PET in neuroendocrine tumors: In vivo applications and in vitro studies
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2000 (engelsk)Inngår i: The Quarterly journal of nuclear medicine, ISSN 1125-0135, Vol. 44, nr 1, s. 68-76Artikkel i tidsskrift (Fagfellevurdert) Published
Abstract [en]

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

Emneord
Gastrointestinal Neoplasms/radionuclide imaging, Humans, Neuroendocrine Tumors/*radionuclide imaging/secondary, Pancreatic Neoplasms/radionuclide imaging, Radiopharmaceuticals/diagnostic use, Research Support; Non-U.S. Gov't, Tomography; Emission-Computed
HSV kategori
Identifikatorer
urn:nbn:se:uu:diva-73665 (URN)10932603 (PubMedID)
Tilgjengelig fra: 2008-05-22 Laget: 2008-05-22 Sist oppdatert: 2017-12-14bibliografisk kontrollert
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