Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0027627 (metastases)
 103,950 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Compared with other imaging modalities and clinical investigation, the 111In-pentetreotide scan identified additional metastatic disease sites in 12 carcinoid patients and 2 occult primaries, and influenced the therapeutic outcome in 36 patients [29 carcinoids, 2 atypical carcinoids, 3 cancers of unknown primaries (CUPs) and 2 medullary thyroid carcinomas (MCTs)]. No adverse reactions were noted. Somatostatin receptors were detected in 59/60 carcinoid patients, 3/4 atypical carcinoid patients, 0/2 MCT patients, and 0/3 cases of CUP. Somatostatin receptor presence is underestimated in some patients using standard hormonal response criteria rather than scintigraphy. 18 patients with metastatic carcinoids who underwent 111In-pentetreotide scanning were all somatostatin receptor positive. Their mean (+/- SE) 5-hydroxyindoleacetic acid (5-HIAA) suppression with octreotide therapy was -53% (+/- 6%). 8 patients had < 50% and 10 had > 50% 5-HIAA suppression (ranges: -4 to -47% and -58 to -94%, respectively). To investigate the effect of somatostatin analogues on survival, 90 consecutive cases of carcinoid syndrome patients treated during the somatostatin analogue era were reviewed. Survival according to primary site was 12.01, 18.29 and 6.05 years (overall median 12.01 years) for patients with foregut, midgut and unknown primaries, respectively. The difference from historical controls is substantial (67 vs. 18% 5-year survival), although our series is neither prospective nor randomised. The heterogeneity in patient and tumour response to somatostatin analogue therapy is discussed.
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PMID:Somatostatin receptor imaging: predictive and prognostic considerations. 881 70

Peptide receptor scintigraphy is more sensitive at the biological than anatomical level, in contrast to conventional imaging, which it complements. Neuroendocrine tumours have the most somatostatin receptors in vitro and their metastases are somatostatin receptor positive in vitro, so that [111In-DTPA-D-Phe1]octreotide (OCT) can be used to image them. OCT was compared with conventional imaging techniques (CON) in a European Multicentre Trial. In 350 evaluable patients, CON detected 88%, and OCT 80% (glucagonomas 100%, VIPomas 88%, carcinoids 87%, non-functioning islet cell tumours 82%, insulinomas 46%) of tumour sites but there was no systematic use of abdominal single-photon-emission computerised tomography. OCT demonstrated multiple tumour sites in 62 of 178 patients in whom CON had found only 1 lesion, with 60% confirmed. 12/16 lesions detected by OCT in 11 patients with no lesions according to CON were also confirmed. The impact of OCT on management was evaluated in 235 patients and affected 40%: it determined 29 surgical decisions, led to octreotide therapy in 47, and modified octreotide dose in 18. Six end-stage patients with neuroendocrine tumours were treated with OCT radionuclide therapy (up to a cumulative dose of 53 GBq per patient) in a phase I trial. There were no major side-effects after up to 2 years treatment, with impressive effects on hormone production and a likely anti-proliferative effect.
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PMID:Somatostatin receptor: scintigraphy and radionuclide therapy. 881 72

A mouse mastocytoma model was used to determine the biodistribution and tumour uptake of four radiopharmaceuticals developed to target the serotonin synthetic pathway in carcinoid tumours. Three of the compounds were competitive inhibitors of the rate-limiting enzyme of serotonin synthesis, tryptophan hydroxylase. Radiolabelled iodo-dL-phenylalanine (iodine-131 PIPA) was found to have the highest uptake and tumour-to-liver ratio. Four patients with known carcinoid tumours were then injected with 0.5 mCi 131I-PIPA and imaged at 1, 4, 24 and 48 h post-injection. The radiopharmaceutical, however, failed to localize in the known tumour sites. This result was in contrast to the authors experience of 131I- and 123I-MIBG imaging of carcinoid tumours. Seven patients with known metastatic carcinoid tumours, two patients with symptoms of recurrence following tumour resection, one patient with completely resected disease, and two patients with a flushing syndrome of uncertain aetiology were studied with 131I-MIBG. Three of the seven patients with known metastatic disease had positive 131I-MIBG scans. Both patients with clinical evidence of recurrent disease had negative scans, as did the patient who was considered to have had complete resection of her primary tumour. The two patients with idiopathic flushing syndrome also had negative scans. Among seven patients imaged with 123I-MIBG there were four true-negative scans and one false-negative, the latter in a patient with biochemical and CT evidence of recurrence. In a seventh patient with distant metastases there was variable uptake in some of the lesions. Four patients were studied with indium-111 pentetreotide . Two patients with metastatic carcinoid disease had positive scans, although hepatic metastases were not seen in one. Another two with idiopathic flushing syndrome had normal studies. The literature suggests that up 50% of carcinoid tumour cases are detected with 131I-MIBG, compared to a sensitivity of 87% reported with somatostatin receptor imaging using 111In-pentetreotide. The experience with 123I-MIBG is much less extensive. The mechanisms of carcinoid tumour localization for each of the three classes of radiotracers are discussed and contrasted to their varying sensitivities. The relative success of 131I-MIBG and 111In-pentetreotide relative to 131I-PIPA may be related to the fact that 131I-MIBG is actively taken up and stored by the enterochromaffin cells of the tumours and 111In-pentetreotide binds to cell surface receptors, whereas 131I-PIPA binds to tryptophan hydroxylase, which may be present in quantities too small to permit tumours to be imaged.
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PMID:Successful and unsuccessful approaches to imaging carcinoids: comparison of a radiolabelled tryptophan hydroxylase inhibitor with a tracer of biogenic amine uptake and storage, and a somatostatin analogue. 892 46

In medullary thyroid cancer (MTC), post-surgically elevated plasma calcitonin and/or carcinoembryonic antigen levels frequently indicate persisting metastatic disease, although conventional diagnostic procedures fail to localize the responsible lesions (occult disease). Somatostatin analogues have been used successfully in disease localization, but recently concerns have been raised that increased thoracic uptake of indium-111 pentetreotide in patients with previous external beam irradiation may represent a false-positive finding, caused by post-irradiation pulmonary fibrosis. We recently examined seven patients with metastatic MTC by somatostatin receptor scintigraphy (six with occult and one with established disease). In four patients, all of whom had stable or slowly rising tumour marker levels over several years, a chimney-like bilateral mediastinal uptake of indium-111 pentetreotide was found. In two patients with persisting hypercalcitonaemia immediately after primary surgery, supraclavicular lymph node metastases were identified as the responsible lesions. None of these seven patients had prior external beam radiation therapy. In two cases, histological confirmation was obtained. In one patient, disease progression could be shown during follow-up. These data suggest that bilateral mediastinal lymph node involvement is a typical site of disease in slowly progressing occult metastatic MTC; the "chimney sign" may represent a typical finding with somatostatin analogues in such cases. Therefore, we believe that even in the case of prior external beam irradiation, mediastinal uptake of octreotide might represent metastatic MTC rather than radiation fibrosis.
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PMID:Enhanced bilateral somatostatin receptor expression in mediastinal lymph nodes ("chimney sign") in occult metastatic medullary thyroid cancer: a typical site of tumour manifestation? 902 Nov 16

Somatostatin is a widely distributed inhibitory peptide with growth-inhibitory effects in several human tumours, including breast cancer, raising the possibility that it may have therapeutic potential. The effects of somatostatin are mediated via a family of cell-surface receptors that differ in their tissue distribution, pharmacological properties and intracellular response mediators, suggesting that they mediate different functions of the peptide. We have analysed the expression of somatostatin receptor subtype (SSTR1-5) mRNA in normal and malignant breast tissue. Receptor expression was analysed by reverse transcription-polymerase chain reaction (RT-PCR) using receptor subtype-specific primers and by in situ hybridization (ISH) with riboprobes synthesized by in vitro transcription of cloned PCR products. A total of 51 breast carcinomas, 36 samples of matched normal tissue, two axillary node metastases and eight normal/benign breast tissue samples were analysed. SSTR2 expression was ubiquitous in both normal and malignant breast tissue. Expression of SSTR5 was detected in approximately one-third of tumour and normal tissue, but fewer than 13% of all tissues expressed SSTR1, 3 and 4. These data suggest that SSTR2 gene expression is ubiquitous in breast cancer. Although this is unlikely to have diagnostic or prognostic significance, SSTR2-specific somatostatin analogues may have therapeutic potential in breast cancer.
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PMID:Analysis of somatostatin receptor subtype mRNA expression in human breast cancer. 906 98

Neuroendocrine tumors are rare and slowly progressing malignancies developing predominantly in the gastrointestinal tract. Often symptoms caused by excessive hormone production lead to diagnosis, especially when active metabolites are released from hepatic metastases to reach the systemic circulation before they are inactivated in the liver. Preoperative diagnosis of specific tumors relies on demonstration of the respective hormones in serum or urine than on histological diagnosis. Localization of primaries or their metastases can be accomplished by CT-AP, somatostatin receptor scintigraphy, SPECT or PET studies with high sensitivity. At the time of diagnosis more than 60% of tumors have already spread to the liver. Potentially curative resection of liver metastases can achieve 5-year survival rates of more than 60%. Since excess hormone production may be incapacitating and even life-threatening, effective palliation is highly important. Five-year survival following palliative liver resection was calculated to be the almost 40%. Palliative liver resection may therefore be considered an alternative to liver transplantation with 5-year survival of 34% in a collected series. If liver resection is not possible, at least temporary palliation of symptoms and retardation of tumor growth can effectively be achieved with somatostatin analogues.
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PMID:[Diagnosis and therapy of liver metastases of neuroendocrine tumors]. 915 77

This study presents the first successful use of a peptidic vector, DOTATOC, labelled with the beta-emitting radioisotope yttrium-90, for the treatment of a patient with somatostatin receptor-positive abdominal metastases of a neuroendocrine carcinoma of unknown localization. Tumour response and symptomatic relief were achieved. In addition, the new substance DOTATOC was labelled with the diagnostic chemical analogue indium-111 and studied in three patients with histopathologically verified neuroendocrine abdominal tumours for its diagnostic sensitivity and compared with the commercially available OctreoScan. In all patients the kidney-to-tumour uptake ratio (in counts per pixel) was on average 1. 9-fold lower with 111In-DOTATOC than with OctreoScan. DOTATOC could be a potential new diagnostic and therapeutic agent in the management of neuroendocrine tumours.
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PMID:DOTATOC: a powerful new tool for receptor-mediated radionuclide therapy. 921 67

Previous studies of the intraoperative use of a hand-held gamma probe to localize metastases and primary tumors of colorectal cancer have shown improved assessment of tumor spread and changes in surgical management based on added information gained by radioimmunoguided surgery. Following the injection of 180 MBq [111In-DTPA-D-Phe1]-pentetreotide and/or 500 MBq 99mTc-dimercaptosuccinic acid (both for dual-radionuclide scintigraphy) preoperative somatostatin receptor imaging [11 patients with GEP tumors] and dual-radionuclide scintigraphy. (8 patients with relapsing medullary thyroid carcinomas) was performed. One patient with a metastasizing pheochromocytoma underwent 123]-MIBg scintigraphy. Results were combined with the information obtained from conventional imaging modalities. Intraoperative radiodetection was performed 24 hours after administration of [111In-DTPA-D-Phe1]-pentetreotide or 4 hours following the injection of 99mTc(V)DMSA using a hand-held gamma probe (Tec Probe 2000. Stratec, FRG). Intraoperative gamma counting localized 39 somatostatin receptor positive lesions of GEP tumors whereas preoperative receptor imaging visualized 81%, surgical palpation 41% and radiological imaging modalities localized only 31%. In 8 patients with recurrent medullary thyroid carcinoma the surgeon was successful in localizing and removing 18 tumor lesions by the help of the gamma probe. Dual-radionuclide scintigraphy revealed 77% (Octreoscan 5/18; 99mTc-V-DMSA 9/18), surgical palpation 55% and conventional imaging methods (CT, sonography) only 38% of all lesions detected intraoperatively by the hand-held gamma probe. In summary, this preliminary data show that intraoperative hand-held gamma probe detection of microscopic and occult endocrine tumors is feasible and more sensitive than external scintigraphy and conventional imaging.
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PMID:[Pre- and intraoperative localization of neuroendocrine tumors]. 927 12

Scintimammography is a recently verified technique that will expand the use of nuclear medicine to a new group of patients in whom scintigraphic imaging has not been widely used. If performed correctly, and in certain groups of patients, it delivers a sensitivity as high as X-ray mammography or magnetic resonance imaging (MRI) in palpable tumours but with greater specificity. It is best used in patients in whom X-ray mammography, ultrasound and MRI prove non-diagnostic or unhelpful, particularly those women with dense breasts or who have had previous breast surgery. The mechanism of uptake of 99Tcm-MIBI in breast tissue is only partly understood and in itself may help in determining important aspects of tumour function, such as the response to cytotoxic chemotherapy. Other scintigraphic methods for imaging breast cancer may be able to look at other aspects of cancer function, for example blood supply, metabolic rate or the in vivo assessment of oestrogen or somatostatin receptor status. This in turn may be useful in planning treatment. Metastatic disease may best be monitored with 18F-FDG PET, which has a sensitivity greater than MRI but a similar specificity. Much furtner work will need to be done on the use of nuclear medicine in breast cancer, but the addition of unique functional information to the anatomical data from X-ray and MRI should benefit future patients' management.
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PMID:Scintigraphic imaging of breast cancer: a review. 929

Scintigraphy using [111In-DTPA-d-Phe1]-pentetreotide or pentavalent technetium-99m-dimercaptosuccinic acid [99mTc(V)-DMSA] has been shown to localize well-differentiated and slowly growing neuroendocrine tumours, whereas increased fluorodeoxyglucose (FDG) uptake is associated with malignancy. The aim of this study was to compare the value of fluorine-18 FDG positron emission tomography (PET) with that of somatostatin receptor scintigraphy (SS-R) and dual-radionuclide scintigraphy [SS-R and 99mTc(V)-DMSA = DNS] in detecting malignant neuroendocrine tumours. Fifteen patients with metastasizing gastroenteropancreatic tumours (GEP tumours; n = 7), medullary thyroid carcinomas (MTCs; n = 8) and elevated tumour markers [GEP tumours: 5-hydroxyindoleacetic acid, insulin; MTCs: calcitonin, carcinoembryonic antigen (CEA)] were studied. Prior to PET, all patients with GEP tumours underwent SS-R. DNS was performed in all patients with MTC. Patients had been fasting for at least 12 h and normal glucose plasma levels were confirmed. Sixty minutes after intravenous administration of 18F-FDG (mean: 374 MBq) whole-body PET and regional scans were performed. In addition, the resected tissues were prepared for immunocytochemistry examination (cell cycle-associated Ki-67 antigen). In two patients with less-differentiated GEP tumours associated with high proliferative activity and increased FDG uptake, SS-R failed to detect any lesion. In comparison, in four patients with well-differentiated GEP tumours showing low proliferative activity, SS-R localized four primary tumours, 22 lymph node metastases and 18 malignant liver lesions, whereas 18F-FDG PET demonstrated normal distribution. In one patient with a metastasizing carcinoid (medium proliferative activity) SS-R localized multiple metastases, whereas PET demonstrated low FDG uptake in all known metastases. In patients with recurrent MTC and rapidly increasing CEA levels DNS detected only three lesions in two patients, whereas PET demonstrated one pulmonary, three osseous, 20 mediastinal, ten locoregional, and four liver metastases in seven patients. Twenty-nine malignant lesions were confirmed by follow-up and nine lymph node metastases could be surgically removed. In conclusion, PET imaging of gastroenteropancreatic tumours revealed increased glucose metabolism only in less-differentiated GEP tumours with high proliferative activity and metastasizing MTC associated with rapidly increasing CEA levels. Therefore, additional 18F-FDG PET should be performed only if SS-R or DNS is negative.
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PMID:Limited value of fluorine-18 fluorodeoxyglucose positron emission tomography for the imaging of neuroendocrine tumours. 939 78


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