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)

In vivo somatostatin receptor-mediated scintigraphy has proven to be a valuable method for the visualisation of neuroendocrine tumours and their metastases. A new application is the use of radiolabelled analogues for somatostatin receptor-mediated therapy. This paper presents a review on the basic science, historical background and current knowledge of somatostatin receptor subtypes and their expression in neuroendocrine tumours. New somatostatin analogues, new chelators, "new" radionuclides and combinations thereof are also discussed. Due attention is given to limitations and future perspectives of somatostatin receptor-mediated imaging and therapy.
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PMID:Somatostatin receptor-mediated imaging and therapy: basic science, current knowledge, limitations and future perspectives. 1158 3

Carcinoid tumors may relapse after a long time span following initial diagnosis, and relapse might be clinically inapparent despite biochemical indications due to a low sensitivity of conventional methods. We present the case of a patient who had biochemical indication for hidden disease persistence for more than two decades. In 1978, a 39-year-old man underwent surgery for a carcinoid tumour of the ileum measuring 3.5 cm with multiple local lymph-node metastases. After surgery, however, serotonin- and urinary 5-hydroxy-indole-acetic-acid (5-HIAA) remained markedly elevated, and persisted over more than 20 years at levels between 600 and 950 ng/ml for serum serotonin (normal range 40-400 ng/ml) and 29-35 mg/24 h for 5-HIAA (normal range 2-9 mg/24 h). Despite this, regular radiological follow-up, including sonography and CT-scan, did not reveal the location of suspected malignancy until 1999, when the patient was re-admitted to our hospital for a hypertensive episode. CT-scanning of the abdomen showed a singular lesion within the liver, which was verified as recurrence of the carcinoid by fine needle biopsy. Somatostatin receptor scintigraphy using (111)In-DTPA-D-Phe1-Octreotide revealed a second lesion within the liver along with local recurrence at the anastomosis, which was verified by surgery. While the propensity for late relapse of ileal carcinoids has repeatedly been demonstrated, a case with biochemical signs of disease persistence over a time span of 21 years before final diagnosis is unusual. In addition, our case reflects the low sensitivity of conventional radiological evaluation for localization of carcinoid tumours as compared to somatostatin receptor scanning.
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PMID:Malignancy in slow motion: diagnosis of biochemically apparent, but otherwise occult persistent disease 21 years after resection of a carcinoid tumour of the terminal ileum. 1158 88

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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PMID:Intraoperative tumour detection using 111In-DTPA-D-Phe1-octreotide and a scintillation detector. 1168 87

Endocrine tumours of the pancreas (ETPs) are rare neoplasms that are frequently malignant. Despite their usual slow growth, metastases do occur and have a major impact on prognosis. Metastases may be the first manifestation of disease, and recognition of particular radiological features of these hypervascular metastases should suggest their possible neuroendocrine origin. Although somatostatin receptor scintigraphy has changed the imaging strategy for these tumours and has become their principal imaging modality, radiological techniques are still required for precise localization of scintigraphic hot spots and monitoring of response to therapy. This pictorial review shows the typical radiological features of ETP metastases and emphasizes the role of different imaging modalities.
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PMID:Imaging appearances of metastases from neuroendocrine tumours of the pancreas. 1170 76

The presence of functional SSR in tumors has several clinical implications which include the possibility a) to control hormonal hypersecretion and related symptomatology by treatment with SS-analogs, b) to detect SSR positive tumors and their metastases by in vivo SSR scintigraphy, and c) to carry out SSR-targeted radiotherapy using radiolabeled SS-analogs. The majority of SSR positive tumors show a differential expression of somatostatin receptor subtypes, sst2 receptors being the most frequently expressed SSR subtype. The predominant expression of sst2 receptors forms the basis for the successful application of sst2 preferring agonists in the treatment of patients with GH-secreting pituitary adenomas, as well as in patients with carcinoid or islet cell tumors. Sst2 and sst5 receptors appear to be differentially involved in the regulation of normal and tumoral pituitary hormone secretion. Additionally, sst2 receptors are involved in the receptor-mediated internalisation of sst2 preferring radiolabeled SS-analogs. The predominant expression of sst2 receptors in neuroendocrine tumors probably determines the successful application of radio-labeled SS-analogs for the detection of primary tumors and their metastases by SSR scintigraphy. In conclusion, the efficacy of treatment with SS-analogs, the visualisation of SSR-positive tumors, as well as the possibility to carry out SSR-targeted radiotherapy, may very well depend upon the density and subtype of SSR that is expressed by the tumors. Therefore, the characterisation of SSR subtypes in human tumors may have important clinical consequences.
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PMID:Somatostatin receptor subtype expression in human tumors. 1176 49

Somatostatin and its octapeptide analogues exert their effects through interaction with somatostatin receptor (sst) subtypes 1 through 5 (sst 1-5 ). Somatostatin binds with high affinity to all sst subtypes, whereas the currently commercially available octapeptide analogues bind only with a high affinity to sst 2 and sst 5. Pituitary tumors, endocrine pancreatic tumors, and carcinoid tumors express multiple sst subtypes, but sst 2 predominance is found in 90% of carcinoids and 80% of endocrine pancreatic tumors. Sst 2 and sst 5 predominance is found in growth hormone-secreting pituitary tumors. In patients harboring sst 2 - or sst 5 -positive neuroendocrine tumors, clinical symptomatology can be controlled by the chronic administration of one of the currently commercially available octapeptide somatostatin analogues. Tumors and metastases that bear sst 2 or sst 5 can be visualized in vivo after injection of radiolabeled octapeptide analogues. Radiolabeled octapeptide analogues can also be used for radiotherapy of sst 2 - and sst 5 -positive advanced or metastatic neuroendocrine tumors.
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PMID:Somatostatin and somatostatin analogues: diagnostic and therapeutic uses. 1179 Sep 81

Merkel cell carcinoma (MCC) is a rare, highly malignant cutaneous tumor, primarily of the head and neck, that requires timely diagnosis, adequate staging, and aggressive therapy. MCC tends to be overlooked in the early stage, has a high propensity for invading local and regional nodal basins, and exhibits a high postoperative recurrence rate, with distant thoracic, abdominal, and central nervous system metastases. Conventional radiography and cross-sectional imaging show lesions similar to those originating from other small cell carcinomas. Nuclear medicine procedures such as sentinel node scintigraphy, somatostatin receptor scintigraphy, and positron emission tomography may be used to supplement judicious cross-sectional imaging evaluation, thereby adding diagnostic value in staging and providing therapeutic guidance. Ultimately, however, the diagnosis relies exclusively on pathologic findings at immunohistochemical staining and electron microscopy. The rarity of MCC and the resulting insufficient awareness of this neoplasm often delay correct identification and treatment, which essentially consists of wide-margin surgical excision of the primary tumor and local and regional radiation therapy. To date, clinical information is still insufficient to fully appreciate the role of imaging in MCC management. A better imaging algorithm is expected with increased awareness and improved clinical understanding of this uncommon skin neoplasm.
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PMID:Imaging of Merkel cell carcinoma. 1189 26

The authors briefly review radiopeptides currently approved for use in the United States. They present a short review of the peptide somatostatin's actions and also note the five somatostatin receptors (SSTRs) to which the peptide and its synthetic analogs octreotide, lanreotide, and vapreotide bind. The many conditions besides neuroendocrine tumors having SSTRs are listed. Labeled octreotide and the other two analogues have a strong affinity for SSTR2 and SSTR5, which thereby produce positive imaging. The various neuroendocrine tumors best imaged by somatostatin receptor scintigraphy (SRS) are discussed, and the exceptions (insulinoma and medullary thyroid carcinoma) are noted to be seen better with labeled VIP and (99m)Tc-dimethylsuccinic acid (DMSA), respectively. SRS and VIP receptor scintigraphy are also noted to image many nonneuroendocrine tumors, which often have appropriate receptors. Several of the currently emerging and very effective new imaging techniques are described. These include (99m)Tc-DMSA for medullary thyroid carcinoma, (18)F dihydroxyphenylalanine positron emission tomography, and C(11) 5-hydroxytryptophan positron emission tomography scanning for all neuroendocrine tumor, but especially carcinoid tumor, metastases. The special role of SRS in identifying gastric carcinoid tumors in hypergastrinemic patients is reviewed. Various pitfalls in interpreting SRS are presented and receptor-enhancing techniques described. Besides use of SRS (mainly Octreoscan, Mallinckrodt Medical, St. Louis, MO) only for detecting and localizing primary tumors and metastases for staging, there are many additional special uses for clinical management of SRS-positive tumors. These include the intraoperative use of the handheld gamma-detecting probe. A brief enumeration is given of the most promising of other non-SST G-protein-coupled receptors and ligands currently under development. Finally, we have posed a number of questions for which answers are needed in the immediate future to facilitate better imaging. Extrapolations of current knowledge and experience with radiolabeled peptide pharmaceutical imaging are converted to reasonable speculations of anticipated future developments in this field.
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PMID:Radiolabeled peptides in diagnosis and tumor imaging: clinical overview. 1196 2

Somatostatin receptors are known to be present at a high density in a large number of tumors while (111)In-DTPA-octreotide has been routinely used in oncology for imaging somatostatin receptor-positive tumors and metastases. Lanreotide is another somatostatin receptor-specific peptide, shown to be effective in controlling the growth of some human tumors. The aim of this study was to label lanreotide with 99mTc by a direct labeling method and to evaluate the distribution and elimination characteristics of the labeled agent in rats. (111)In-octreotide was used as the reference radiopharmaceutical. For both radiolabeled-peptides the activity in blood and most organs decreased relatively rapidly with time. On the other hand, 99mTc-lanreotide was excreted mainly by the gastrointestinal tract to feces while (111)In-DTPA-octreotide was eliminated mostly into urine. The rat liver perfusion experiments showed that bile clearance of 99mTc-lanreotide was about three-order times higher than for (111)In-DTPA-octreotide. Analysis of the elimination mechanisms of 99mTc-lanreotide and (111)In-DTPA-octreotide in the perfused rat kidney confirmed that both peptides were eliminated mostly by glomerular filtration. Different protein binding of the agents ((111)In-DTPA-octreotide was only weakly bound, whereas 99mTc-lanreotide was strongly bound to proteins) resulted in substantially lower renal clearance of 99mTc-lanreotide when compared with (111)In-DTPA-octreotide. The results indicated that 99mTc-lanreotide could be of value for the scintigraphic imaging of specific tumors.
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PMID:Lanreotide labeled with 99mTc: preparation, preclinical testing and comparison with (111)In-DTPA-octreotide. 1217 93

12 women with primary breast cancer underwent somatostatin receptor scintigraphy (SRS) with 111In-DTPA-D-Phe1-octreotide. The tumour sizes varied between 2 and 5 cm and were all, except one, palpable at clinical examination. Tumour biopsies were taken with additional sampling from normal breast tissue, fat, muscle, axillary lymph nodes and peripheral blood. Ratios between the 111In activity concentration in the tissue biopsies (Ti) and in peripheral blood (B) as well as in normal breast tissue (Br) were calculated. In 8/12 patients the scintillation detector was used intraoperatively for radioactivity measurements of the biopsies in situ and ex vivo. The sstr-subtype profiles were determined by northern blot analysis and the relative expression of sstr2 by ribonuclease protection assay (RPA) and immunocytochemistry. Preoperative SRS visualised all primary breast cancer tumours. The scintigraphic image showed no correlation with the histopathological type of the tumour or with the abundance of oestrogen/progesterone receptors on the tumour. Two patients with a massive tumour infiltration of the lymph nodes had a distinct positive SRS of the ipsilateral axilla. In one patient with three nodal metastases the scintigraphic image of the axilla was weak but visible. Four other patients with a negative axillary scintigraphy had 1-2 lymph node metastases. The Ti/B ratios for the breast tumours varied between four and 33 and were not different from Ti/Br ratios. In lymph node metastases the Ti/B ratios were higher (10-41). Intraoperative detector measurements showed a significant difference between the breast tumour and normal tissue in 2/8 patients in situ. Similar measurements on excised tissues (ex vivo) showed a significant difference in 6/8 patients. Two patients with lymph node metastases exhibited a significantly increased uptake ex vivo by detector measurements, but in only one of them in situ. All tumour biopsies expressed the presence of sstrl, 3, 4 and 5, but not of sstr2 at northern analysis. On the other hand, sstr2 was detected in all tumours by RPA and immunocytochemistry. Preoperative SRS visualised primary breast cancer lesions in all 12 patients. SRS could also demonstrate extensive axillary tumour infiltration. Intraoperative use of the scintillation detector could not exclude axillary metastases in situ. The low Ti/B values of both primary tumours and metastases indicate limitations of the radiopharmaceutical used.
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PMID:Indium-111-octreotide scintigraphy, intraoperative gamma-detector localisation and somatostatin receptor expression in primary human breast cancer. 1218 70


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