| 1. |
- Ekeblad, Sara, et al.
(författare)
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Temozolomide as monotherapy is effective in treatment of advanced malignant neuroendocrine tumors
- 2007
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Ingår i: Clinical Cancer Research. - 1078-0432 .- 1557-3265. ; 13:10, s. 2986-2991
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: A retrospective analysis of the toxicity and efficacy of temozolomide in advanced neuroendocrine tumors. Experimental Design: Thirty-six patients with advanced stages of neuroendocrine tumor (1 gastric, 7 thymic and 13 bronchial carcinoids, 12 pancreatic endocrine tumors, 1 paraganglioma, 1 neuroendocrine foregut, and 1 neuroendocrine cecal cancer) were treated with temozolomide (200 mg/m2) for 5 days every 4 weeks. Patients had previously received a mean of 2.4 antitumoral medical regimens. Tumor response was evaluated radiologically according to the Response Evaluation Criteria in Solid Tumors every 3 months on an intent-to-treat basis. The circulating tumor marker plasma chromogranin A was also assessed. The expression of 06-methylguanine DNA methyltransferase, an enzyme implicated in chemotherapy resistance, was studied by immunohistochemistry (n = 23) and compared with response to temozolomide. Results: Median overall time to progression was 7 months (95% confidence interval, 3-10). Radiologic response was seen in 14% of patients and stable disease in 53%. Side effects were mainly hematologic; 14% experienced grade 3 or 4 thrombocytopenia (National Cancer Institute toxicity criteria). Ten patients had tumors with 06-methylguanine DNA methyltransferase immunoreactivity in <10% of nuclei, whereas four patients showed radiologic responses. Conclusions: Temozolomide as monotherapy had acceptable toxicity and antitumoral effects in a small series of patients with advanced malignant neuroendocrine tumors and four of these showed radiologic responses.
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| 2. |
- Eriksson, Barbro, et al.
(författare)
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Developments in PET for the detection of endocrine tumours
- 2005
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Ingår i: Baillière's Best Practice & Research. Clinical Endocrinology & Metabolism. - : Elsevier BV. - 1521-690X .- 1532-1908. ; 19:2, s. 311-324
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- 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.
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| 3. |
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| 4. |
- Eriksson, B, et al.
(författare)
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[PET in neuroendocrine tumors].
- 1998
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Ingår i: Nordisk Medicin. - 0029-1420. ; 113:9, s. 308-312
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Tidskriftsartikel (refereegranskat)abstract
- With the radionuclide tracers available today, 50-90 per cent of neuroendocrine tumours of the gastro-intestinal tract can be visualised with PET (positron-emission tomography). PET also enables the effect of tumour treatment to be monitored in terms of biochemical and functional variables, which is not possible with other radiological techniques. Owing to the very good tumour resolution possible with PET, it serves as a complement to other routine methods such as computed tomography and ultrasonography, and can be used to screen the chest and abdomen for small primary tumours that can not be detected with other methods. In several pre-operative trials PET has been shown to demonstrate more changes in the pancreas and liver than was possible with other methods. In the near future it will be possible to demonstrate the presence of and quantify growth factor receptors, hormones, enzymes, DNA synthesis, mRNA synthesis and protein synthesis. Access to these tumour biological data will be of crucial importance to the individualisation of treatment.
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| 5. |
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| 6. |
- Eriksson, Barbro, et al.
(författare)
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Positron emission tomography in neuroendocrine tumours
- 1999
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Ingår i: The Italian Journal of Gastroenterology and Hepatology. - 1125-8055. ; Suppl 2, s. S167-S171
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Tidskriftsartikel (refereegranskat)abstract
- Positron emission tomography is an in vivo tracer and imaging technique that utilizes short-lived positron emitting radionuclides (11C, 15O, 13N, 18F) with half-lives ranging between 2 min and 2 hours. These radionuclides are interesting from the labelling viewpoint since they are natural constituents of most biologically active compounds. The short half-life is an advantage with regard to the irradiation dose to the patient but it is also a limitation since it requires the production of these radionuclides in close vicinity to the positron emission tomography camera.
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| 7. |
- Eriksson, Barbro, et al.
(författare)
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The role of PET in localization of neuroendocrine and adrenocortical tumors
- 2002
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Ingår i: Annals of the New York Academy of Sciences. - : Wiley. - 0077-8923 .- 1749-6632. ; 970, s. 159-169
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Tidskriftsartikel (refereegranskat)abstract
- 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.
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| 8. |
- Eriksson, Barbro, et al.
(författare)
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Use of PET in neuroendocrine tumors : In vivo applications and in vitro studies
- 2000
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Ingår i: The Quarterly journal of nuclear medicine. - 1125-0135. ; 44:1, s. 68-76
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Tidskriftsartikel (refereegranskat)abstract
- 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.
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| 9. |
- Granberg, Dan, et al.
(författare)
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Gastrin-releasing-peptide in neuroendorine tumours
- 2006
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Ingår i: Acta Oncologica. - : Informa UK Limited. - 0284-186X .- 1651-226X. ; 45:1, s. 23-27
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Tidskriftsartikel (refereegranskat)abstract
- 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?
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| 10. |
- Sundin, Anders, et al.
(författare)
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PET in the diagnosis of neuroendocrine tumors
- 2004
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Ingår i: Annals of the New York Academy of Sciences. - : Wiley. - 0077-8923 .- 1749-6632. ; 1014, s. 246-257
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Tidskriftsartikel (refereegranskat)abstract
- 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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