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Somatostatin receptors on intestinal carcinoid tumor. Fig. 3. Somatostatin receptors in an ovarian carcinoid tumor. A: Hematoxylin-eosin stained section. B: Autoradiogram showing A: Hematoxylin-eosin stained section. Bar = I mm. B: Autoradiototal binding of '*'I-Tyr'-SMS 201-995. C: Autoradiogram showgram showing total binding of 'Z51-Tyr'-SMS 201-995. C: Auing non-specific binding (in the presence of I pmol/l Tyr'-SMS toradiogram showing non-specific binding (in the presence of 201-995). Bar = 1 mm. 1 pmol/l Tyr3-SMS 201-995).
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![Fig. 6. '231-[Tyr3]-SMS 201-995 scan of an SS receptor-positive tumor...](profile/Larry-Kvols/publication/21505349/figure/fig4/AS:601614008188935@1520447365318/231-Tyr3-SMS-201-995-scan-of-an-SS-receptor-positive-tumor-in-vivo-Anterior-abdominal_Q320.jpg)
High affinity somatostatin receptors (SS-R) have been identified in membrane homogenates or tissue sections from several hundred human tumors. SS-R were found in most tumors originating from SS target tissues, i.e. GH and TSH producing pituitary tumors, endocrine gastroenteropancreatic (GEP) tumors and brain tumors. SS-R were also expressed in seve...
Context in source publication
Context 1
... very high incidence of homogeneously distributed SS receptors is found in most hormone-producing gastroen- teropancreatic (GEP) tumors ( shown in Fig. 2. Interestingly, most of the SS receptor negative carcinoids belong to the less differentiated atypical carcinoids. These are often bronchial carcinoids, whereas intestinal carcinoids usually are receptor positive (6). Also, carcinoids from other origin are positive, as the ovarian carcinoid in Fig. 3. Also most of the islet cell ...
Citations
... Apart from normal tissues, the expression of SRIF system components concerns a range of human cancers [16,17,19,48,53], mainly NENs/NETs of GI tract [45,107,[121][122][123]. SST-producing NETs are derived mostly from the pancreas, duodenum, and small intestine [124][125][126]. Most of well-differentiated gastroenteropancreatic endocrine carcinomas (WDEC) also demonstrate the presence of SSTRs, mainly SST2 (including SST2A) and SST5 [121,122,126,127]. However, the most prominent SST subtype, detected in GEP-NETs, is SST2/SST2A, identified in >70% of cases at a high expression intensity [45,47,121,122,128,129]. ...
... However, the most prominent SST subtype, detected in GEP-NETs, is SST2/SST2A, identified in >70% of cases at a high expression intensity [45,47,121,122,128,129]. The occurrence of a high density of SSTRs has prognostic significance and may be used in the therapy of these cancers [45,47,126,127,129]. ...
Somatostatin (SST)/somatotropin release-inhibiting factor (SRIF) is a well-known neuropeptide, widely distributed in the central and peripheral nervous systems, that regulates the endocrine system and affects neurotransmission via interaction with five SST receptors (SST1-5). In the gastrointestinal tract, the main SST-producing cells include intestinal enteroendocrine cells (EECs) restricted to the mucosa, and neurons of the submucosal and myenteric plexuses. The action of the SRIF system is based on the inhibition of endocrine and exocrine secretion, as well as the proliferative responses of target cells. The SST1–5 share common signaling pathways, and are not only widely expressed on normal tissues, but also frequently overexpressed by several tumors, particularly neuroendocrine neoplasms (NENs). Furthermore, the SRIF system represents the only peptide/G protein-coupled receptor (GPCR) system with multiple approved clinical applications for the diagnosis and treatment of several NENs. The role of the SRIF system in the histogenesis of colorectal cancer (CRC) subtypes (e.g., adenocarcinoma and signet ring-cell carcinoma), as well as diagnosis and prognosis of mixed adenoneuroendocrine carcinoma (MANEC) and pure adenocarcinoma, is poorly understood. Moreover, the impact of the SRIF system signaling on CRC cell proliferation and its potential role in the progression of this cancer remains unknown. Therefore, this review summarizes the recent collective knowledge and understanding of the clinical significance of the SRIF system signaling in CRC, aiming to evaluate the potential role of its components in CRC histogenesis, diagnosis, and potential therapy.
... SSTRs are predominantly expressed by human central nervous system (CNS) and neuroendocrine tumors [246]. However, several cancers, including breast [247][248][249], lung [250,251], some colorectal, and ovarian cancers show high SSTR expression [252]. Despite the high affinity of native somatostatin towards SSTRs, its clinical use was hampered by the need of intravenous administration, short half-life, and post-infusion hypersecretion of hormones [253]. ...
Cancer is one of the leading causes of death worldwide. The development of cancer-specific diagnostic agents and anticancer toxins would improve patient survival. The current and standard types of medical care for cancer patients, including surgery, radiotherapy, and chemotherapy, are not able to treat all cancers. A new treatment strategy utilizing tumor targeting peptides to selectively deliver drugs or applicable active agents to solid tumors is becoming a promising approach. In this review, we discuss the different tumor-homing peptides discovered through combinatorial library screening, as well as native active peptides. The different structure–function relationship data that have been used to improve the peptide’s activity and conjugation strategies are highlighted.
... In endocrine tumors, the presence of SSTRs are associated with well differentiation, low grade tumor and good response to somatostatin analog (octreotide) treatment (12,13). ...
... While most well-differentiated endocrine tumors and islet cell carcinomas are SSTR-positive, and therefore responsive to somatostatin analog therapy; the poorly differentiated endocrine tumors are generally SSTRnegative and hardly benefit from somatostatin analog therapy (12,13,14,15). ...
The diagnostic value of somatostatin receptor scintigraphy (SRS) in detecting tumors has been assessed in a number of studies.
We present a 30-year-old female with a history of eight months cough and left shoulder pain. Radiologic evaluation showed
pulmonary mass and hepatic lesions, which were pathologically diagnosed as neuroendocrine carcinoma. 99mTc-octreotide
scan demonstrated that the pulmonary lesion was positive for somatostatin receptor (SSTR), while the liver metastases were
SSTR negative. The present case highlights the significance of a differential uptake pattern by somatostatin receptors in SRS
in patients with neuroendocrine tumors.
... The sensitivity and specificity of 99m Tc-Hynic TOC planar or SPECT/ CT for metastatic disease was 100% and 86%, respectively. This high sensitivity is consistent with high affinity somatostatin binding sites which have been found in vitro on most gastroenteropancreatic endocrine tumors (39,40). The majority of these tumors contain high numbers of receptors homogeneously distributed throughout the tumor site. ...
Objective(s): The objective of this study was to evaluate the performance and utility of 99mTc HYNIC-TOC planar scintigraphy and SPECT/CT in the diagnosis, staging and management of gastroenteropancreatic neuroendocrine tumors (GPNETs).
Methods: 22 patients (median age, 46 years) with histologically proven gastroentero-pancreatic NETs underwent 99mTc HYNIC-TOC whole body scintigraphy and regional SPECT/CT as indicated. Scanning was performed after injection of 370-550 MBq (10-15 mCi) of 99mTc HYNIC-TOC intravenously. Images were evaluated by two experienced nuclear medicine physicians both qualitatively as well as semi quantitatively (tumor to background and tumor to normal liver ratios on SPECT -CT images). Results of SPECT/CT were compared with the results of conventional imaging. Histopathology results and follow-up somatostatin receptor scintigraphy with 99mTc HYNIC TOC or conventional imaging with biochemical markers were considered to be the reference standards.
Results: 99mTc HYNIC TOC showed sensitivity and specificity of 87.5% and 85.7%, respectively, for primary tumor and 100% and 86% for metastases. It was better than conventional imaging modalities for the detection of both primary tumor (P<0.001) and metastases (P<0.0001). It changed the management strategy in 6 patients (31.8%) and supported management decisions in 8 patients (36.3%).
Conclusion: 99mTc HYNIC TOC SPECT/CT appears to be a highly sensitive and specific modality for the detection and staging of GPNETs. It is better than conventional imaging for the evaluation of GPNETs and can have a significant impact on patient management and planning further therapeutic options.
... The majority of these tumors contain high number of SSTRs, homogeneously distributed throughout the tumor, and expressed at both primary and metastatic sites. [24] The utility of 68 Ga-DOTA peptide PET/CT is well-established and can influence many aspects of GEP-NET management including staging patients with already diagnosed NETs, detection of sites of recurrence in patients with treated NETs (restaging), diagnosis of patients suspected of having NET based on clinical features or biochemical evidence of hormone excess, selection of potential candidates for cold somatostatin analogue or peptide receptor radionuclide therapy (PRRT), and monitoring response to therapy in such patients. ...
Neuroendocrine tumors (NETs) are rare neoplasms characterized by overexpression of somatostatin receptors (SSTRs). Functional imaging plays a crucial role in management of NETs. Recently, positron emission tomography/computed tomography (PET/CT) with (68)Gallium ((68)Ga)-labeled somatostatin analogues has shown excellent results for imaging of NETs and better results than conventional SSTR scintigraphy. In this review we have discussed the utility of (68)Ga-labeled somatostatin analogue PET/CT in NETs for various established and potential indications. In addition we have also shared our own experience from a tertiary care center in India.
... The sensitivity and specificity of 68 Ga-DOTA-NOC PET/CT for metastatic disease was 97.4% and 100%, respectively. The high rate of positivity obtained with in vivo 68 Ga-DOTA-NOC PET/CT is not surprising because high-affinity somatostatin-binding sites have been found in vitro on most gastroenteropancreatic endocrine tumors [32,33]. The majority of these tumors contain high numbers of receptors homogeneously distributed throughout the tumor and expressed on both the primary and metastatic sites [32]. ...
Objective:
Similar to neuroendocrine tumors (NETs) at other sites, a wide array of intracranial tumors also express somatostatin receptors (SSTRs). This expression can be exploited for both imaging and therapy. The introduction of (68)Ga-labeled tetraazacyclododecanetetraacetic acid (DOTA)-peptide PET/CT has given new dimension to SSTR-based imaging because of its improved sensitivity and excellent spatial resolution.
Conclusion:
However, in contrast to gastropancreatic and bronchopulmonary NETs, limited literature is available regarding the use of (68)Ga-DOTA-peptide PET/CT in intracranial tumors. Here, we briefly review the available literature and highlight the potential role that (68)Ga-DOTA-peptide PET/CT can play in the management of intracranial tumors.
... Somatostatin is also secreted along the central nervous system and digestive tract, to regulate the production and secretion of pituitary and gastrointestinal hormones, respectively [39]. Tumors arising from these neuroendocrine cells often express one SSTR receptor family member, commonly SSTR2 [40], providing an avenue for ligand-directed imaging and therapeutic opportunities [41][42][43][44][45][46][47][48][49]. The half-life of circulating somatostatin is less than 3 minutes [50], eliminating its utility as a targeting agent and necessitating the development of synthetic analogs for clinical applications [51]. ...
Human pancreatic neuroendocrine tumors are rare tumors that form in the endocrine pancreas. Patients with these tumors have limited therapeutic options, and curative intervention is limited to surgical resection. These tumors do, however, consistently express somatostatin receptor type 2 (SSTR2) making them vulnerable to somatostatin analogs. Exploiting cell surface receptors overexpressed in tumors is a common avenue for ligand-directed delivery of imaging or therapeutic agents to tumors. In this regard, identification of novel ligand/receptor pairs with combinatorial peptide libraries has produced multiple candidates for clinical translation. Alternatively, here, we introduce a hybrid vector of adeno-associated virus and phage (AAVP) displaying a known, rationally chosen, biologically active peptide for the delivery of tumor necrosis factor (TNF). Our ligand, octreotide, is a somatostatin analog with specific affinity for SSTR2 that is currently used clinically for both imaging studies and the relief of symptoms associated with pancreatic neuroendocrine tumors. When displayed in AAVP, octreotide mediates selective internalization of the viral particles after systemic administration. We validated the internalization and transduction capabilities of the octreotide-targeted AAVP in a neuroendocrine tumor cell line expressing SSTR2. Additionally, we confirmed AAVP homing and TNF expression in vivo in a transgenic mouse model of pancreatic neuroendocrine tumor development that mimics human disease. With further investigation, therapeutic gene delivery using the octreotide/SSTR2 ligand/receptor pair could represent a viable clinical alternative for patients lacking adequate treatment options.
... This case might suggest the different biology of primary lesions and their metastases in terms of the expression of GLP-1 receptors. This phenomenon is well known for somatostatin receptors in neuroendocrine tumours [20]. ...
Purpose
The objective of this article is to present a new method for the diagnosis of insulinoma with the use of [Lys40(Ahx-HYNIC-99mTc/EDDA)NH2]-exendin-4.
Methods
Studies were performed in 11 patients with negative results of all available non-isotopic diagnostic methods (8 with symptoms of insulinoma, 2 with malignant insulinoma and 1 with nesidioblastosis). In all patients glucagon-like peptide-1 (GLP-1) receptor imaging (whole-body and single photon emission computed tomography/CT examinations) after the injection of 740 MBq of the tracer was performed.
Results
Both sensitivity and specificity of GLP-1 receptor imaging were assessed to be 100 % in patients with benign insulinoma. In all eight cases with suspicion of insulinoma a focal uptake in the pancreas was found. In six patients surgical excision of the tumour was performed (type G1 tumours were confirmed histopathologically). In one patient surgical treatment is planned. One patient was disqualified from surgery. In one case with malignant insulinoma pathological accumulation of the tracer was found only in the region of local recurrence. The GLP-1 study was negative in the other malignant insulinoma patient. In one case with suspicion of nesidioblastosis, a focal accumulation of the tracer was observed and histopathology revealed coexistence of insulinoma and nesidioblastosis.
Conclusion
[Lys40(Ahx-HYNIC-99mTc/EDDA)NH2]-exendin-4 seems to be a promising diagnostic tool in the localization of small insulinoma tumours, but requires verification in a larger series of patients.
... The sensitivity and specificity of 68 Ga- DOTA-NOC PET/CT for metastatic disease was 97.4% and 100%, respectively. The high rate of positivity obtained with in vivo 68 Ga- DOTA-NOC PET/CT is not surprising because high-affinity somatostatin-binding sites have been found in vitro on most gastroenteropancreatic endocrine tumors [32, 33]. The majority of these tumors contain high numbers of receptors homogeneously distributed throughout the tumor and expressed on both the primary and metastatic sites [32]. ...
The objective of this study was to evaluate the role of (68)Ga-labeled [1, 4, 7, 10-tetraazacyclododecane-1, 4, 7, 10-tetraacetic acid]-1-NaI(3)-octreotide (DOTA-NOC) PET/CT in the diagnosis and management of gastroenteropancreatic neuroendocrine tumors (NETs).
One hundred nine patients (median age, 50 years) with gastroenteropancreatic NETs underwent (68)Ga-DOTA-NOC PET/CT. PET/CT was performed after injection of 132-222 MBq (4-6 mCi) of (68)Ga-DOTA-NOC. Images were evaluated by two experienced nuclear medicine physicians both qualitatively as well as quantitatively (maximum standardized uptake value [SUV(max)]). Results of PET/CT were compared with the results of conventional imaging. Histopathology results, when available, and follow-up PET/CT or conventional imaging with biochemical markers were considered to be the reference standards.
Gallium-68-DOTA-NOC PET/CT showed sensitivity and specificity of 78.3% and 92.5%, respectively, for primary tumor and 97.4% and 100% for metastases. It was better than a conventional imaging modality for the detection of both primary tumor (p < 0.001) and metastases (p < 0.0001). It changed the management strategy in 21 patients (19%) and supported management decisions in 32 patients (29%).
Gallium-68-DOTA-NOC PET/CT appears to be a highly sensitive and specific modality for the detection of gastroenteropancreatic NET. It is better than conventional imaging for the evaluation of gastroenteropancreatic NETs and can have a significant impact on patient management.
... 7 SSTR-1, -2, -4 and -5 induce G 1 cell cycle growth arrest, while SSTR-3 is proapoptotic via the induction of p53 and BAX. 8,9 These subtypes have been identified in human ETs and other tumors and their metastases, using a variety of techniques including autoradiography, 10,11 reverse-transcriptase polymerase chain reaction, and immunohistochemistry (IHC). 12,13 In ETs, the expression of SSTRs correlates with the degree of endocrine differentiation, lower histopathologic tumor grades, 11 and clinical response to somatostatin analog (octreotide) therapy. ...
... 8,9 These subtypes have been identified in human ETs and other tumors and their metastases, using a variety of techniques including autoradiography, 10,11 reverse-transcriptase polymerase chain reaction, and immunohistochemistry (IHC). 12,13 In ETs, the expression of SSTRs correlates with the degree of endocrine differentiation, lower histopathologic tumor grades, 11 and clinical response to somatostatin analog (octreotide) therapy. 6 While the majority of well-differentiated ETs and islet cell carcinomas are SSTR-positive, thus improving their response to somatostatin analog therapy, the poorly differentiated ETs are usually SSTR-negative 11 and rarely respond to somatostatin analog therapy. ...
... 12,13 In ETs, the expression of SSTRs correlates with the degree of endocrine differentiation, lower histopathologic tumor grades, 11 and clinical response to somatostatin analog (octreotide) therapy. 6 While the majority of well-differentiated ETs and islet cell carcinomas are SSTR-positive, thus improving their response to somatostatin analog therapy, the poorly differentiated ETs are usually SSTR-negative 11 and rarely respond to somatostatin analog therapy. ...
The expression of somatostatin receptors (SSTRs) on endocrine tumor (ET) cells forms the basis for somatostatin analog treatment of patients with SSTR-positive, hormonally active ETs. In patients with SSTR-negative ETs, the clinical response is generally absent or suboptimal, while nonfunctioning ETs with SSTR positivity show a variable response to such therapy.
We retrospectively studied SSTR subtype expression in hepatic metastases from 14 adult patients with primary endocrine carcinomas (ECAs) of the small intestine and pancreas and compared SSTR subtype expression among the primary and metastatic ECAs. Polyclonal antibodies against the 5 SSTR subtypes were used on formalin-fixed, paraffin sections from each primary and metastatic ECA. Both qualitative and semiquantitative evaluation of the stained ECA sections was carried out.
Eleven (61%) of 18 hepatic metastases from small intestinal and pancreatic ECAs were positive for SSTR-1, 15 (83%) for SSTR-2, 13 (72%) for SSTR-3, 10 (56%) for SSTR-4, and 15 (83%) for SSTR-5. Among 11 hepatic ECA metastases from small intestinal ECAs (carcinoids), 7 (63%) expressed SSTR-1, 9 (81%) expressed SSTR-2, 8 (72%) expressed SSTR-3, 6 (54%) expressed SSTR-4, and 10 (91%) expressed SSTR-5. Of 7 hepatic ECA metastases from pancreatic ECAs, 4 expressed SSTR-1, 6 expressed SSTR-2, and 5 expressed SSTR-3 and SSTR-5 each. We also observed the immunohistochemical evidence of heterogeneity of expression of various SSTR subtypes in the primary enteropancreatic ECAs and their hepatic metastases.
SSTR subtype expression needs to be correlated to somatostatin analog therapy. Immunohistochemical profiling of various SSTR subtypes as a part of routine surgical pathologic analysis of enteropancreatic ETs may become a useful predictor of responsiveness of ETs to various SSTR analogs.
