| 1. |
- Forssell-Aronsson, Eva, 1961, et al.
(författare)
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Biodistribution data from 100 patients i.v. injected with 111In-DTPA-D-Phe1-octreotide
- 2004
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Ingår i: Acta oncologica (Stockholm, Sweden). - : Informa UK Limited. - 0284-186X .- 1651-226X. ; 43:5, s. 436-42
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Tidskriftsartikel (refereegranskat)abstract
- The aim of this study was to obtain accurate data on the biodistribution of 111In-DTPA-D-Phe1-octreotide in tumour and normal tissues to facilitate dosimetric evaluations. Patients with carcinoid tumours, medullary thyroid carcinoma (MTC), differentiated thyroid tumours, endocrine pancreatic tumour (EPT), breast carcinoma, and various other tumour types were i.v. injected with 111In-DTPA-D-Phe-1-octreotide. Tumour and normal tissue samples were collected during surgery 1-35 days later, and the 111In activity concentration determined. Results showed large inter- and intra-individual variations. The 111In concentration was in general higher in carcinoids and some EPT (range 0.33-77% IA/kg) than in MTC and other tumours (0.017-7.8% IA/kg). Tumour-to-blood ratios (T/B) higher than 100 were found in most patients with carcinoids, EPT, renal carcinoma, and neuroendocrine carcinoma (max value 1500), while T/B was below 80 in most other tumours. Normal-tissue-to-blood ratios were in general < or = 10 but higher values were found in liver, kidneys, and spleen. The results presented are important for dosimetric calculations, when radiolabelled octreotide is used for diagnostic or therapeutic purposes.
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| 2. |
- Ahlman, Håkan, 1947, et al.
(författare)
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Liver transplantation for treatment of metastatic neuroendocrine tumors
- 2004
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Ingår i: Annals of the New York Academy of Sciences. - 0077-8923. ; 1014, s. 265-9
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Tidskriftsartikel (refereegranskat)abstract
- Liver transplantation can be considered a therapeutic option for patients with neuroendocrine tumors only metastatic to the liver. Important selection criteria are well-differentiated tumors and a low proliferation rate (Ki67 <10%). In this series, orthopic liver transplantation offered good relief of symptoms and long disease-free intervals with initial survival of grafts and patients as in benign disease. The experience with multivisceral transplantation is still limited.
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| 3. |
- Hashemi, S H, et al.
(författare)
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111In-labelled octreotide binding by the somatostatin receptor subtype 2 in neuroendocrine tumours.
- 2003
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Ingår i: The British journal of surgery. - : Oxford University Press (OUP). - 0007-1323 .- 1365-2168. ; 90:5, s. 549-54
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Tidskriftsartikel (refereegranskat)abstract
- The aim of this study was to investigate the importance of somatostatin receptor subtype 2 (SSTR2) expression for 111In-labelled diethylenetriamine-pentaacetic acid (DTPA)-D-Phe1-octreotide binding and uptake of 111In in neuroendocrine tumours.
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| 4. |
- Jakobsen, A M, et al.
(författare)
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Differential expression of vesicular monoamine transporter (VMAT) 1 and 2 in gastrointestinal endocrine tumours.
- 2001
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Ingår i: The Journal of pathology. - : Wiley. - 0022-3417. ; 195:4, s. 463-72
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Tidskriftsartikel (refereegranskat)abstract
- Neuroendocrine tumours are characterized by their capacity to produce hormones, which are stored in vesicles and secretory granules. Demonstration of granule/vesicle proteins in tumours is taken as evidence of neuroendocrine differentiation. Vesicular monoamine transporters (VMAT1 and VMAT2) mediate the transport of amines into vesicles of neurons and endocrine cells. The expression of VMAT1 and VMAT2 and the usefulness of VMAT1 and VMAT2 in the histopathological diagnosis of gastrointestinal endocrine tumours have not been fully explored. This study therefore investigated the expression of VMAT1 and VMAT2 in 211 human gastrointestinal tumours by immunocytochemistry and western blotting. VMAT1 and/or VMAT2 were demonstrated in the majority of amine-producing endocrine tumours of gastric, ileal, and appendiceal origin. Serotonin-producing endocrine tumours (ileal and appendiceal carcinoids) expressed predominantly VMAT1, while histamine-producing endocrine tumours (gastric carcinoids) expressed VMAT2 almost exclusively. In peptide-producing endocrine tumours such as rectal carcinoids and endocrine pancreatic tumours, only a small number of immunopositive tumour cells were observed. No labelling was found in non-endocrine tumours, including gastric, colorectal and pancreatic adenocarcinomas and gastrointestinal stromal tumours. In conclusion, VMAT1 and VMAT2 are differentially expressed by gastrointestinal endocrine tumours, with a pattern specific for each tumour type, reflecting their neuroendocrine differentiation and origin. VMAT1 and VMAT2 may therefore become valuable markers in the classification of neuroendocrine tumours and may also indicate patients suitable for radioisotope treatment operating via these transporter systems.
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| 5. |
- Kölby, Lars, 1963, et al.
(författare)
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Uptake of meta-iodobenzylguanidine in neuroendocrine tumours is mediated by vesicular monoamine transporters.
- 2003
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Ingår i: British journal of cancer. - : Springer Science and Business Media LLC. - 0007-0920 .- 1532-1827. ; 89:7, s. 1383-8
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Tidskriftsartikel (refereegranskat)abstract
- The radio-iodinated noradrenaline analogue meta-iodobenzylguanidine (MIBG) can be used for scintigraphy and radiation therapy of neuroendocrine (NE). The aim of the present study was to study the importance of vesicular monoamine transporters (VMATs) for the uptake of (123)I-MIBG in NE tumours. In nude mice, bearing the human transplantable midgut carcinoid GOT1, all organs and xenografted tumours accumulated (123)I after i.v. injection of (123)I-MIBG. A high concentration of (123)I was maintained in GOT1 tumours and adrenals, which expressed VMATs, but rapidly decreased in all other tissues. In the VMAT-expressing NE tumour cell lines GOT1 and BON and in VMAT-expressing primary NE tumour cell cultures (carcinoids, n=4 and pheochromocytomas, n=4), reserpine significantly reduced the uptake of (123)I-MIBG. The membrane pump inhibitor clomipramine had no effect on the uptake of (123)I-MIBG in GOT1 and BON cells, but inhibited the uptake in one out of four primary carcinoid cell cultures and three out of four primary pheochromocytoma cell cultures. In conclusion, VMATs and secretory granules are of importance for the uptake and retention of (123)I-MIBG in NE tumours. Information about the type and degree of expression of VMATs in NE tumours may be helpful in future to select patients suitable for radiation therapy with radio-iodinated MIBG.
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| 6. |
- Benjegård, S A, et al.
(författare)
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Intraoperative tumour detection using 111In-DTPA-D-Phe1-octreotide and a scintillation detector.
- 2001
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Ingår i: European journal of nuclear medicine. - : Springer Science and Business Media LLC. - 0340-6997 .- 1619-7070 .- 1619-7089. ; 28:10, s. 1456-62
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Tidskriftsartikel (refereegranskat)abstract
- Intraoperative tumour detection has been used in many applications. The examined tumour forms have varied and different detector systems and radiopharmaceuticals have also been used. The aim of this study was to evaluate and compare the ability of an NaI(T1) scintillation detector to detect primary tumours and metastases in patients with different endocrine tumour types (e.g. carcinoid tumours, endocrine pancreatic tumours and thyroid tumours) and in patients with breast carcinoma or benign thyroid lesions, on the basis of their somatostatin receptor expression after i.v. injection of 111In-DTPA-D-Phe1-octreotide. Thirty patients were injected with 111In-DTPA-D-Phe1-octreotide intravenously. Scintigraphic images were taken 1 day after injection of the radiopharmaceutical, and surgery was performed 1-7 days post injection. An NaI(T1) scintillation detector was used for intraoperative tumour detection. Tissue samples were collected during surgery for determination of 111In activity concentration and histopathological examination. The scintigraphic images were positive in 29 out of 30 patients. Intraoperative tumour detection was successful in 43 of 66 collected biopsies: 10 out of 11 for carcinoid tumours, 7 out of 10 for medullary thyroid carcinoma (MTC) and 14 out of 22 for breast cancer. On the basis of our findings we conclude that intraoperative tumour detection with 111In-DTPA-D-Phe1-octreotide using this NaI(T1) detector can be successful especially for carcinoid tumours and endocrine pancreatic tumours, due to the relatively high activity concentrations in these tumour types, but is less successful in other forms of thyroid cancer, including MTC, and breast cancer. For successful intraoperative detection, the detector characteristics are also very important, and further improvement of the detector systems is required to increase the sensitivity and specificity.
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| 7. |
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| 8. |
- Kölby, Lars, 1963, et al.
(författare)
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A transplantable human carcinoid as model for somatostatin receptor-mediated and amine transporter-mediated radionuclide uptake.
- 2001
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Ingår i: The American journal of pathology. - 0002-9440. ; 158:2, s. 745-55
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Tidskriftsartikel (refereegranskat)abstract
- A human midgut carcinoid tumor was successfully transplanted into nude mice and propagated for five consecutive generations (30 months) with well-preserved phenotype. Tumor cells in nude mice expressed identical neuroendocrine markers as the original tumor, including somatostatin receptors (somatostatin receptors 1 to 5) and vesicular monoamine transporters (VMAT1 and VMAT2). Because of the expression of somatostatin receptors and VMAT1 and VMAT2 the grafted tumors could be visualized scintigraphically using the somatostatin analogue 111In-octreotide and the catecholamine analogue 123I-metaiodobenzylguanidine. The biokinetics of the somatostatin analogue 111In-octreotide in the tumors was studied and showed a high retention 7 days after administration. Cell cultures were re-established from transplanted tumors. Immunocytochemical and ultrastructural studies confirmed the neuroendocrine differentiation. The human origin of transplanted tumor cells was confirmed by cytogenetic and fluorescence it situ hybridization analyses. Spontaneous secretion of serotonin and its metabolite, 5-hydroxyindole acetic acid, from tumor cells was demonstrated. The tumor cells increased their [Ca2+]i in response to beta-adrenoceptor stimulation (isoproterenol) and K+-depolarization. All somatostatin receptor subtypes could be demonstrated in cultured cells. This human transplantable carcinoid tumor, designated GOT1, grafted to nude mice, will give unique possibilities for studies of somatostatin receptor- and VMAT-mediated radionuclide uptake as well as for studies of secretory mechanisms.
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| 9. |
- Levin Jakobsen, Anne-Marie, 1955, et al.
(författare)
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Expression of synaptic vesicle protein 2 (SV2) in neuroendocrine tumours of the gastrointestinal tract and pancreas.
- 2002
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Ingår i: The Journal of pathology. - : Wiley. - 0022-3417. ; 196:1, s. 44-50
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Tidskriftsartikel (refereegranskat)abstract
- Identification of neuroendocrine differentiation in tumours has important implications for prognosis and therapy. The aim of the present study was to evaluate monoclonal antibodies against synaptic vesicle protein 2 (SV2) as histopathological markers for neuroendocrine differentiation in tumours of the gastrointestinal tract and pancreas. Paraffin blocks from 211 gastrointestinal tumours were examined by immunocytochemistry, using a monoclonal antibody against SV2. Virtually all endocrine tumours of the gastrointestinal tract (11/11 gastric, 53/53 ileal, 16/21 appendiceal, and 22/22 rectal) and pancreas (24/24) were positively labelled. SV2 labelling was also demonstrated in gastrointestinal pacemaker cell tumours (8/8), while adenocarcinomas of the gastrointestinal tract and pancreas were negative, with the exception of occasional adenocarcinomas demonstrating weak SV2 labelling (stomach 1/22, rectum 1/29, and pancreas 0/21). Western blotting of tumour biopsies confirmed expression of SV2 in endocrine tumours of the gastrointestinal tract and pancreas. No relationship was observed between SV2 expression in tumours and hormone production or malignant potential. In conclusion, SV2 is expressed in neuroendocrine tumours of the gastrointestinal tract and pancreas, but not in non-endocrine tumours. The SV2 monoclonal antibody can therefore be used as a general marker for neuroendocrine differentiation in gastrointestinal and pancreatic tumours.
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| 10. |
- Olausson, Michael, 1956, et al.
(författare)
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Indications and results of liver transplantation in patients with neuroendocrine tumors.
- 2002
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Ingår i: World journal of surgery. - : Springer Science and Business Media LLC. - 0364-2313 .- 1432-2323. ; 26:8, s. 998-1004
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Tidskriftsartikel (refereegranskat)abstract
- Metastases from neuroendocrine (NE) tumors of the gastrointestinal tract, carcinoids, and endocrine pancreatic tumors (EPTs) can be confined to the liver for long periods and may exhibit slow growth. When considering liver transplantation (LTx) for patients with NE tumors, the expected results with conventional treatment must be weighed against the risk of LTx and immunosuppression. The following indications for LTx may be considered for patients with metastatic NE tumors limited to the liver: (1) tumors not accessible to curative surgery or major tumor reduction; (2) tumors not responding to medical or interventional treatment; and (3) tumors causing life-threatening hormonal symptoms. We excluded patients with poorly differentiated NE carcinoma or well differentiated NE carcinoma with a high proliferation index (Ki 67 > 10%). Over 4 years (1997-2001) we have performed transplants in nine patients (five with EPTs, four with carcinoids) with a mean +/- SEM follow-up of 22 +/- 5 months (range 4-45 months). Seven patients underwent orthotopic LTx and two multivisceral LTx. Eight patients are alive, six without clinical evidence of disease. Four patients developed recurrent tumors 9 to 36 months after LTx; two were detected at an early stage and underwent resection with curative intent. One patient with multivisceral Tx died after 4 months of posttransplant lymphoproliferative disease without tumor recurrence. In selected series LTx can offer good control of hormonal symptoms, a relatively long disease-free interval, and in individual cases potential cure.
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