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Nuclear Medicine Review. Central &... 2016The aim of this review is to summarize the developments and briefly characterize the somatostatin analogs which are currently used for somatostatin receptor imaging in... (Review)
Review
The aim of this review is to summarize the developments and briefly characterize the somatostatin analogs which are currently used for somatostatin receptor imaging in clinical routine or in early phase clinical trials. Somatostatin (sst) receptor targeting with radiolabeled peptides has become an integral part in nuclear oncology during the last 20 years. This integration process has been initiated in Europe with the introduction to the market of 111In-DTPA-DPhe1-octreotide [111In-pentetreotide]. Introducing 99mTc in somatostatin receptor targeting radiopeptides resulted in much better image quality, higher sensitivity of tumor detection and lower mean effective dose for the examined patient. The next generation are 68Ga labeled somatostatin analogs. Due to the spatial resolution of PET technique and increasing number of PET scanners, the PET or PET/CT technique became very important in somatostatin receptor imaging. Until up to a couple of years ago the analogs of somatostatin were constructed aiming at their agonistic behavior, expecting that their internalization with the receptor acti-vated by the radiolabeled ligand and its retention within the tumor cell are crucial for efficient imaging and therapy. Recently it has been shown that the antagonists recognize more binding sites at the tumor cell membrane and hence offer an improved diagnostic efficacy, especially when the density of sst receptors is low. This approach may in future improve diagnostic value of somatostatin receptor imaging techniques. The developments in tracer design are followed by the improvements in imaging techniques. The new SPECT scanners offer resolution close to that of PET, which might open a new era for 99mTc and other SPECT radiotracers.
Topics: Drug Stability; Humans; Molecular Imaging; Neuroendocrine Tumors; Radiopharmaceuticals; Receptors, Somatostatin; Somatostatin
PubMed: 27479790
DOI: 10.5603/NMR.2016.0024 -
PET Clinics Apr 2021PET/computed tomography (CT) imaging increasingly is used in neuroendocrine neoplasms (NENs) for diagnosis, staging, monitoring, prognostication, and choosing treatment.... (Review)
Review
PET/computed tomography (CT) imaging increasingly is used in neuroendocrine neoplasms (NENs) for diagnosis, staging, monitoring, prognostication, and choosing treatment. Somatostatin PET analog tracers have added to the specificity by obtaining higher affinity to somatostatin receptors with Ga-labeled or Cu-labeled DOTA peptides compared with single-photon emission CT imaging isotopes. PET uptake correlates to tumor grade and is an essential part of theranostics with peptide receptor radionuclide treatment. This article focuses on the literature on head-to-head studies and meta-analyses of different combinations of peptide agonists and a few antagonists. Overall, the published data support the diagnostic capability of PET/CT imaging in NENs.
Topics: Humans; Neuroendocrine Tumors; Organometallic Compounds; Positron Emission Tomography Computed Tomography; Positron-Emission Tomography; Radiopharmaceuticals; Receptors, Somatostatin
PubMed: 33648664
DOI: 10.1016/j.cpet.2020.12.011 -
Frontiers in Endocrinology 2022The treatment options that are currently available for management of metastatic, progressive radioactive iodine (RAI)-refractory differentiated thyroid cancers (DTCs),... (Review)
Review
The treatment options that are currently available for management of metastatic, progressive radioactive iodine (RAI)-refractory differentiated thyroid cancers (DTCs), and medullary thyroid cancers (MTCs) are limited. While there are several systemic targeted therapies, such as tyrosine kinase inhibitors, that are being evaluated and implemented in the treatment of these cancers, such therapies are associated with serious, sometimes life-threatening, adverse events. Peptide receptor radionuclide therapy (PRRT) has the potential to be an effective and safe modality for treating patients with somatostatin receptor (SSTR)+ RAI-refractory DTCs and MTCs. MTCs and certain sub-types of RAI-refractory DTCs, such as Hürthle cell cancers which are less responsive to conventional modalities of treatment, have demonstrated a favorable response to treatment with PRRT. While the current literature offers hope for utilization of PRRT in thyroid cancer, several areas of this field remain to be investigated further, especially head-to-head comparisons with other systemic targeted therapies. In this review, we provide a comprehensive outlook on the current translational and clinical data on the use of various PRRTs, including diagnostic utility of somatostatin analogs, theranostic properties of PRRT, and the potential areas for future research.
Topics: Carcinoma, Neuroendocrine; Humans; Iodine Radioisotopes; Receptors, Somatostatin; Thyroid Neoplasms
PubMed: 35712243
DOI: 10.3389/fendo.2022.896287 -
Seminars in Nuclear Medicine Sep 2016Somatostatin receptor PET/CT using (68)Ga-labeled somatostatin analogs, is a mainstay for the evaluation of the somatostatin receptor status in neuroendocrine neoplasms.... (Review)
Review
Somatostatin receptor PET/CT using (68)Ga-labeled somatostatin analogs, is a mainstay for the evaluation of the somatostatin receptor status in neuroendocrine neoplasms. In addition, the assessment of glucose metabolism by (18)F-FDG PET/CT at diagnosis can overcome probable shortcomings of histopathologic grading. This offers a systematic theranostic approach for the management of neuroendocrine neoplasms, that is, patient selection for the appropriate treatment-surgery, somatostatin analogs, peptide receptor radionuclide therapy, targeted therapies like everolimus and sunitinib, or chemotherapy-and also for therapy response monitoring. Novel targets, for example, the chemokine receptor CXCR4 in higher-grade tumors and glucagon like peptide-1 receptor in insulinomas, appear promising for imaging. Scandium-44 and Copper-64, especially on account of their longer half-life (for pretherapeutic dosimetry) and cyclotron production (which favors mass production), might be the potential alternatives to (68)Ga for PET/CT imaging. The future of molecular imaging lies in Radiomics, that is, qualitative and quantitative characterization of tumor phenotypes in correlation with tumor genomics and proteomics, for a personalized cancer management.
Topics: Humans; Neuroendocrine Tumors; Positron Emission Tomography Computed Tomography; Receptors, Somatostatin
PubMed: 27553465
DOI: 10.1053/j.semnuclmed.2016.06.001 -
International Journal of Molecular... Jan 2022Somatostatin (SST) is a small peptide that exerts inhibitory effects on a wide range of neuroendocrine cells. Due to the fact that somatostatin regulates cell growth and... (Review)
Review
Somatostatin (SST) is a small peptide that exerts inhibitory effects on a wide range of neuroendocrine cells. Due to the fact that somatostatin regulates cell growth and hormone secretion, somatostatin receptors (SSTRs) have become valuable targets for the treatment of different types of neuroendocrine tumours (NETs). NETs are a heterogeneous group of tumours that can develop in various parts of the body, including the digestive system, lungs, and pituitary. NETs are usually slow growing, but they are often diagnosed in advanced stages and can display aggressive behaviour. The mortality rate of NETs is not outstandingly increased compared to other malignant tumours, even in the metastatic setting. One of the intrinsic properties of NETs is the expression of SSTRs that serve as drug targets for SST analogues (SSAs), which can delay tumour progression and downregulate hormone overproduction. Additionally, in many NETs, it has been demonstrated that the SSTR expression level provides a prognostic value in predicting a therapeutic response. Furthermore, higher a SSTR expression correlates with a better survival rate in NET patients. In recent studies, other epigenetic regulators affecting SST signalling or SSA-mTOR inhibitor combination therapy in NETs have been considered as novel strategies for tumour control. In conclusion, SST signalling is a relevant regulator of NET functionality. Alongside classical SSA treatment regimens, future advanced therapies and treatment modalities are expected to improve the disease outcomes and overall health of NET patients.
Topics: Humans; Neoplasm Metastasis; Neuroendocrine Tumors; Prognosis; Receptors, Somatostatin; Signal Transduction; Somatostatin; Survival Rate
PubMed: 35163374
DOI: 10.3390/ijms23031447 -
Frontiers in Endocrinology 2021Somatostatin (SST) and somatostatin receptors (SSTRs) play an important role in the brain and gastrointestinal (GI) system. SST is produced in various organs and cells,... (Review)
Review
Somatostatin (SST) and somatostatin receptors (SSTRs) play an important role in the brain and gastrointestinal (GI) system. SST is produced in various organs and cells, and the inhibitory function of somatostatin-containing cells is involved in a range of physiological functions and pathological modifications. The GI system is the largest endocrine organ for digestion and absorption, SST-endocrine cells and neurons in the GI system are a critical effecter to maintain homeostasis SSTRs 1-5 and co-receptors, while SST-SSTRs are involved in chemo-sensory, mucus, and hormone secretion, motility, inflammation response, itch, and pain the autocrine, paracrine, endocrine, and exoendocrine pathways. It is also a power inhibitor for tumor cell proliferation, severe inflammation, and post-operation complications, and is a first-line anti-cancer drug in clinical practice. This mini review focuses on the current function of producing SST endocrine cells and local neurons SST-SSTRs in the GI system, discusses new development prognostic markers, phosphate-specific antibodies, and molecular imaging emerging in diagnostics and therapy, and summarizes the mechanism of the SST family in basic research and clinical practice. Understanding of endocrines and neuroendocrines in SST-SSTRs in GI will provide an insight into advanced medicine in basic and clinical research.
Topics: Animals; Antineoplastic Agents; Cell Communication; Cell Proliferation; Disease Models, Animal; Enteric Nervous System; Gastrointestinal Tract; Homeostasis; Humans; Inflammation; Ligands; Neurons; Parasympathetic Nervous System; Prognosis; Receptors, Somatostatin; Somatostatin; Somatostatin-Secreting Cells; Sympathetic Nervous System
PubMed: 33796080
DOI: 10.3389/fendo.2021.652363 -
Frontiers in Endocrinology 2022Congenital hyperinsulinism (CHI), although a rare disease, is an important cause of severe hypoglycemia in early infancy and childhood, causing preventable morbidity and... (Review)
Review
Congenital hyperinsulinism (CHI), although a rare disease, is an important cause of severe hypoglycemia in early infancy and childhood, causing preventable morbidity and mortality. Prompt diagnosis and appropriate treatment is necessary to prevent hypoglycaemia mediated brain damage. At present, the medical treatment of CHI is limited to diazoxide as first line and synthetic somatostatin receptor ligands (SRLs) as second line options; therefore understanding somatostatin biology and treatment perspectives is important. Under healthy conditions, somatostatin secreted from pancreatic islet δ-cells reduces insulin release through somatostatin receptor induced cAMP-mediated downregulation and paracrine inhibition of β- cells. Several SRLs with extended duration of action are now commercially available and are being used off-label in CHI patients. Efficacy remains variable with the present generation of SRLs, with treatment effect often being compromised by loss of initial response and adverse effects such as bowel ischaemia and hepatobiliary dysfunction. In this review we have addressed the biology of the somatostatin system contexualised to CHI. We have discussed the clinical use, limitations, and complications of somatostatin agonists and new and emerging therapies for CHI.
Topics: Biology; Child; Congenital Hyperinsulinism; Diazoxide; Humans; Insulin; Ligands; Receptors, Somatostatin; Somatostatin
PubMed: 36237195
DOI: 10.3389/fendo.2022.921357 -
PET Clinics Jul 2024Neuroendocrine neoplasms (NEN) are rare tumors arising from neuroendocrine cells. NEN are ideally suited for a theragnostic approach due to their specific expression of... (Review)
Review
Neuroendocrine neoplasms (NEN) are rare tumors arising from neuroendocrine cells. NEN are ideally suited for a theragnostic approach due to their specific expression of somatostatin receptors (SSTR). SSTR imaging of NEN dates back to the 1980s, but has evolved recently due to the introduction of more sensitive SSTR PET radiotracers. SSTR PET is a primary imaging modality for identifying NEN and characterizing SSTR expression. SSTR PET is complementary to anatomic imaging for assessing tumor response to treatment. SSTR PET is mandated to determine eligibility for peptide receptor radionuclide therapy. Here, the role of imaging to aid management of NEN is reviewed.
Topics: Humans; Neuroendocrine Tumors; Receptors, Somatostatin; Positron-Emission Tomography; Radiopharmaceuticals; Positron Emission Tomography Computed Tomography
PubMed: 38714399
DOI: 10.1016/j.cpet.2024.03.008 -
Archives of Medical Research Dec 2023Treatment strategies for NFPA include surgery, radiotherapy, medical treatment, or follow-up. The treatment of NFPAs with compressive symptoms is surgical. However, in... (Review)
Review
Treatment strategies for NFPA include surgery, radiotherapy, medical treatment, or follow-up. The treatment of NFPAs with compressive symptoms is surgical. However, in case of post-surgical tumor remnants, there may be treatment strategies that include observation and radiotherapy. Recently, medical treatment with cabergoline (CAB) has been recommended to contain and/or reduce the size of the tumor remnant. Based on the findings that many NFPAs show a dopamine receptor (DR) and somatostatin receptor (SR) expression, medical therapy with dopamine agonists (DAs) and somatostatin receptor ligands (SSRLs) has been tested as an alternative to prevent recurrence after surgery. The DAs have been the most extensively studied, showing some potential in terms of tumor shrinkage. SSRLs and other emerging medical options are much less studied. We will review and critically evaluate the current data on the medical therapy of NFPAs to elucidate their role in the management of this tumor type. In the case of actively growing remnants (more than 10% growth per year) and high-risk pituitary adenomas, treatment with CAB at a dose of 1.5-3.0 mg is indicated for tumor containment and/or reduction. In relation to combined chemotherapy with CAB, there is little information in the literature to support its use. In our experience, CAB treatment can be used after radiotherapy as an adjuvant treatment.
Topics: Humans; Pituitary Neoplasms; Receptors, Somatostatin; Adenoma; Receptors, Dopamine
PubMed: 37996269
DOI: 10.1016/j.arcmed.2023.102917 -
Islets Dec 2023Somatostatin is a paracrine modulator of insulin secretion and beta cell function with pleotropic effects on glucose homeostasis. The mechanism of somatostatin-mediated...
Somatostatin is a paracrine modulator of insulin secretion and beta cell function with pleotropic effects on glucose homeostasis. The mechanism of somatostatin-mediated communication between delta and beta cells is not well-understood, which we address in this study via the ciliary somatostatin receptor 3 (SSTR3). Primary cilia are membrane organelles that act as signaling hubs in islets by virtue of their subcellular location and enrichment in signaling proteins such as G-protein coupled receptors (GPCRs). We show that SSTR3, a ciliary GPCR, mediates somatostatin suppression of insulin secretion in mouse islets. Quantitative analysis of calcium flux using a mouse model of genetically encoded beta cell-specific GCaMP6f calcium reporter shows that somatostatin signaling alters beta cell calcium flux after physiologic glucose stimulation, an effect that depends on endogenous SSTR3 expression and the presence of intact primary cilia on beta cells. Comparative studies using SSTR isoform antagonists demonstrate a role for SSTR3 in mediating somatostatin regulation of insulin secretion in mouse islets. Our findings support a model in which ciliary SSTR3 mediates a distinct pathway of delta-to-beta cell regulatory crosstalk and may serve as a target for paracrine modulation.
Topics: Cilia; Glucose; Receptors, Somatostatin; Somatostatin; Animals; Mice
PubMed: 37660302
DOI: 10.1080/19382014.2023.2252855