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Medical Principles and Practice :... 2012Molecular imaging is defined as the visualization, characterization, and measurement of biological processes at the molecular and cellular levels in humans and other... (Review)
Review
Molecular imaging is defined as the visualization, characterization, and measurement of biological processes at the molecular and cellular levels in humans and other living systems. Most clinical molecular imaging is currently done using radioisotope-labeled agents to define the activity of various metabolic pathways in vivo or to determine the distribution and density of various receptors relevant to human disease. This paper briefly reviews most of the commonly used radiopharmaceuticals in nuclear medicine, as well as newer agents that are likely to become available in the near future. The metabolic pathways include those relevant to the thyroid, parathyroid, heart, brain, bones, kidneys, liver, pancreas, adrenals and tumor. The receptor systems include agents useful in evaluating movement disorders, dementia, cardiac sympathetic enervation and neoangiogenesis. Receptor systems relevant to tumors include somatostatin receptors (neuroendocrine tumors), prostate-specific membrane antigen, carbonic anhydrase IX (renal cancer), and CD-20 (lymphoma). These agents, and newer agents that are being developed, are likely to become critical in the development of personalized medicine, where it will become increasingly important to determine whether a treatment that is targeted to a specific metabolic pathway or receptor is likely to be successful.
Topics: Humans; Molecular Imaging; Neoplasms; Nuclear Medicine; Receptors, Somatostatin
PubMed: 22142905
DOI: 10.1159/000333552 -
Annals of Nuclear Medicine Oct 2018Both prostate-specific membrane antigen (PSMA)- and somatostatin receptor (SSTR)-targeted positron emission tomography (PET)-based imaging agents for prostate carcinoma... (Review)
Review
Both prostate-specific membrane antigen (PSMA)- and somatostatin receptor (SSTR)-targeted positron emission tomography (PET)-based imaging agents for prostate carcinoma and neuroendocrine tumors, respectively, are seeing rapidly expanding use. In addition to diagnostic applications, both classes of radiotracers can be used to triage patients for theranostic endoradiotherapy. While interpreting PSMA- or SSTR-targeted PET/computed tomography (CT) scans, the reader has to be aware of certain pitfalls. Adding to the complexity of the interpretation of those imaging agents, both normal biodistribution, and also false-positive and -negative findings differ between PSMA- and SSTR-targeted PET radiotracers. Herein summarized under the umbrella term molecular imaging reporting and data systems (MI-RADS), two novel RADS classifications for PSMA- and SSTR-targeted PET imaging are described (PSMA- and SSTR-RADS). Notably, PSMA- and SSTR-RADS are structured in a reciprocal fashion, i.e., if the reader is familiar with one system, the other system can readily be applied, as well. In the present review, we will discuss the most common pitfalls on PSMA- and SSTR-targeted PET/CT, briefly introduce PSMA- and SSTR-RADS, and define a potential future role of the umbrella framework MI-RADS compared to other classification systems.
Topics: Antigens, Surface; Diagnostic Imaging; Glutamate Carboxypeptidase II; Humans; Radioactive Tracers; Radiotherapy; Receptors, Somatostatin; Research Design
PubMed: 30109562
DOI: 10.1007/s12149-018-1291-7 -
Annals of Oncology : Official Journal... 1999Genes for five somatostatin receptor subtypes, designated sst1-5, have been cloned and shown to belong to the seven transmembrane domain receptor family. The sst2 mRNA... (Review)
Review
Genes for five somatostatin receptor subtypes, designated sst1-5, have been cloned and shown to belong to the seven transmembrane domain receptor family. The sst2 mRNA transcript is alternatively spliced to generate two related receptor products (sst2A and sst2B) which differ in their carboxylterminal sequence whereas each of the other genes is transcribed to give a single unique receptor protein. The six sst receptor subtypes all bind SRIF14, SRIF28 and the cortistatins with high affinity but vary in their affinity for analogs, such as octreotide. Although the tissue distribution of sst mRNAs has been extensively examined, much less is known about the cellular distribution of the individual receptor proteins. Recent studies with sst subtype specific antibodies have localized individual sst receptors to specific cell types within the rat gastrointestinal tract, pancreas, pituitary and brain. Furthermore, sst receptors have recently been identified in human tumors by immunocytochemistry, providing a significantly improved method for sst receptor detection. All six sst receptor subtypes are linked to guanine nucleotide binding proteins (G proteins) and lead to inhibition of adenylyl cyclase following hormone binding. The sst receptors also regulate a variety of different effectors via G proteins, including calcium and potassium channels and serine and tyrosine phosphatases. In addition to signalling, two other processes are activated by hormone binding: receptor desensitization and receptor internalization. The extent to which these occur seems to vary for the different receptor subtypes. Recent studies have shown that the sst2A receptor is rapidly phosphorylated upon hormone binding, suggesting that this phosphorylation may be responsible for the desensitization and/or internalization of this receptor. The importance of receptor regulation in cellular responsiveness to somatostatin and for receptor detection as well as the molecular mechanisms by which these processes occur provide important areas for future investigations.
Topics: Animals; Forecasting; Humans; Receptors, Somatostatin
PubMed: 10399028
DOI: 10.1093/annonc/10.suppl_2.s17 -
Alimentary Pharmacology & Therapeutics Aug 2003Somatostatin and its analogue octreotide have been used for two decades to treat oesophageal variceal haemorrhage. The drug was introduced because of its capacity to... (Review)
Review
Somatostatin and its analogue octreotide have been used for two decades to treat oesophageal variceal haemorrhage. The drug was introduced because of its capacity to decrease portal venous pressure without major side effects. In clinical trials assessing the efficacy of somatostatin and long-acting analogues in arresting variceal haemorrhage, conflicting results have been obtained. Furthermore, in haemodynamic studies evaluating the effects of somatostatin and analogues in patients with cirrhosis, divergent effects were observed. The main reason for these differences is probably related to different affinities of the drugs for different somatostatin receptor subtypes. The effects of somatostatin and analogues are mediated via five different G-protein coupled receptors (somatostatin receptor subtypes 1-5), which regulate the activity of ion channels (Ca2+, K+, Na+ and Cl-) and enzymes (adenyl cyclase, phospholipase C, phospholipase A2, phosphoinositide 3-kinase and guanylate cyclase) responsible for the synthesis or degradation of intracellular second messengers including cyclic AMP, inositol 1,4,5-trisphosphate, diacylglycerol and cyclic GMP. Despite universal use of somatostatin, the cellular and biochemical mechanisms of its effects in portal hypertension are relatively poorly studied and remain incompletely understood. In this review, we summarize relevant signal transduction of somatostatin and analogues, the haemodynamic effects of the drugs and the possible mechanisms by which these effects are mediated.
Topics: Blood Flow Velocity; Blood Pressure; Hormones; Humans; Hypertension, Portal; Receptors, Somatostatin; Somatostatin
PubMed: 12940922
DOI: 10.1046/j.1365-2036.2003.01657.x -
Medical Science Monitor : International... Apr 2017BACKGROUND Thyrotropin-secreting pituitary adenomas (TSHomas) are a rare cause of hyperthyroidism. Somatostatin analogs have proved to be effective for inhibiting...
BACKGROUND Thyrotropin-secreting pituitary adenomas (TSHomas) are a rare cause of hyperthyroidism. Somatostatin analogs have proved to be effective for inhibiting pituitary hormones secretion, working via interactions with somatostatin receptors (SSTRs). Moreover, antiproliferative activity of somatostatin analog is now demonstrated in several studies. In the present study, we determined the relative predominance of SSTR2 and SSTR5 subtypes among the different types of adenomas, especially TSHoma, and investigated the relationship between efficacy of short-term octreotide (OCT) treatment and SSTR expression. MATERIAL AND METHODS Serum hormone determinations and histological findings in resected tissue resulted in 5 diagnoses: 16 TSHomas, 8 acromegaly, 3 prolactinomas, 3 corticotropinomas, 4 clinically nonfunctioning adenomas (NFPAs), and 4 normal pituitary specimens. IHC was performed on formalin-fixed and paraffin-embedded tissue in tissue microarrays. RESULTS IHC of SSTR subtypes in the different cohorts showed SSTR2 staining intensity scores higher than SSTR5 in TSHoma, acromegaly and prolactinoma, whereas the expression of SSTR5 was stronger than SSTR2 in corticotropinoma and NFPA. SSTR2 and SSTR5 expressions were significantly higher in TSHoma than in other pituitary adenomas. OCT treatment for a median of 8.4 days (range: 3-18 days) and with a total median dose of 1.9 mg (range: 0.9-4.2 mg) showed a significant decrease of thyroid hormone levels (TSH [μIU/ml] in all patients. Patients with low SSTR5 expression presented a significantly higher TSH suppression rate (P values <0.05). CONCLUSIONS The present data confirm that somatostatin analogs should be considered as a medical alternative to surgical treatment, especially in patients with TSHoma, and short-term response to OCT therapy may be related to the expression of SSTR5.
Topics: Adolescent; Adult; Aged; Female; Humans; Hyperthyroidism; Male; Middle Aged; Pituitary Neoplasms; RNA, Messenger; Receptors, Somatostatin; Somatostatin; Thyrotropin
PubMed: 28434012
DOI: 10.12659/msm.903377 -
Journal of Nuclear Medicine : Official... Feb 2020PET/CT with Ga-DOTA-somatostatin analogs has been tested for therapy monitoring in patients with neuroendocrine tumors (NETs). However, SUVs in tumors do not correlate...
PET/CT with Ga-DOTA-somatostatin analogs has been tested for therapy monitoring in patients with neuroendocrine tumors (NETs). However, SUVs in tumors do not correlate with the net influx rate (K), as a representation of the somatostatin receptor expression. In this study, tumor-to-blood ratio (TBR) was evaluated as an alternative tool for semiquantitative assessment of Ga-DOTATOC and Ga-DOTATATE tumor uptake and as a therapy monitoring tool for patients with NETs. Twenty-two NET patients underwent a 45-min dynamic PET/CT scan after injection of Ga-DOTATOC or Ga-DOTATATE. K was determined using the Patlak method, and TBR was calculated for the 40- to 45-min interval. A linear relation was found between K and TBR, with a square of Pearson correlation of 0.98 and 0.93 for Ga-DOTATOC and Ga-DOTATATE, respectively. A high correlation was found between K and TBR. Hence, TBR reflects somatostatin receptor density more accurately than SUV and is suggested as the preferred metric for semiquantitative assessment of Ga-DOTATOC and Ga-DOTATATE tumor uptake.
Topics: Aged; Aged, 80 and over; Female; Humans; Male; Middle Aged; Neuroendocrine Tumors; Octreotide; Organometallic Compounds; Positron Emission Tomography Computed Tomography; Receptors, Somatostatin
PubMed: 31302632
DOI: 10.2967/jnumed.119.228072 -
Annals of Oncology : Official Journal... 2001Exchange of information occurs between cells of neuroendocrine and immune systems. Neuroendocrine hormones may modulate lymphoid cell activities, including proliferation... (Review)
Review
Exchange of information occurs between cells of neuroendocrine and immune systems. Neuroendocrine hormones may modulate lymphoid cell activities, including proliferation and mitogenesis, and immune cells may produce neuropeptides as well. Neuropetide Y is synthesized in B-cell leukaemia lymphoblasts, while substance P immunoreactivity has been detected in neoplastic haematological samples of different types of leukaemias. The presence of receptors for neuropeptides on different animal and human lymphoid cell lines, as well as in several types of animal and human lymphoproliferative diseases has been demonstrated. Species variability in receptor distribution has been shown as well. Receptor expression in immune cells may be regulated by changes in microenvironmental conditions, it may also be related to the activation and/ or proliferation state of cells. Vasoactive intestinal peptides receptors have been detected in myeloma cells, while somatostatin receptors have been first detected in vitro on resting lymphocytes and cells of the monocyte/macrophage lineage, and later on human activated lymphocytes and on lymphoblastic leukaemia cells. Somatostatin receptors have been found in biopsies from patients with malignant lymphomas. Tumor localization in non-Hodgkin lymphomas and Hodgkin's disease can be visualized by in vivo somatostatin receptor scintigraphy, contributing to establish the diagnosis and the stage of the disease. Recently. somatostatin receptors have been in vivo and in vitro detected in human thymic tumors. Although treatment of lymphoproliferative diseases with somatostatin analogs is a little explored field, partial remission was found in patients with low-grade non-Hodgkin lymphoma and cutaneous T-cell lymphoma, and a successful treatment with octreotide has been reported in patients with thymoma. Specific somatostatin receptors present in progenitors of immune cells are not expressed in the mature phenotype, while they can be detected in transformed cell lines. The possibility that this phenomenon is caused by oncogene expression cannot be ruled out. Moreover, preliminary data showed a developmental expression of somatostatin receptors in lymphoid cells, suggesting a potential role for neuropeptide receptors as differentiation markers. Although controlled studies are warranted to investigate the efficacy of the currently available analogs, somatostatinergic compounds may be of interest in the treatment of lymphoproliferative malignancies. A promising approach in refractory patients with somatostatin receptor positive malignant lymphomas may be radionuclide-targeted and cytotoxic analog therapy. These concepts increase the possibility of a wider antitumor treatment with ligands for neuroepeptide receptors than in established 'classic' neuroendocrine tumors.
Topics: Cell Differentiation; Gene Expression Regulation; Humans; Immune System; Leukemia; Lymphocytes; Lymphoma; Neuropeptides; Neurosecretory Systems; Oncogenes; Receptors, Neuropeptide; Receptors, Somatostatin
PubMed: 11762338
DOI: 10.1093/annonc/12.suppl_2.s125 -
The Journal of Biological Chemistry Mar 2000The existence of receptor dimers has been proposed for several G protein-coupled receptors. However, the question of whether G protein-coupled receptor dimers are...
The existence of receptor dimers has been proposed for several G protein-coupled receptors. However, the question of whether G protein-coupled receptor dimers are necessary for activating or modulating normal receptor function is unclear. We address this question with somatostatin receptors (SSTRs) of which there are five distinct subtypes. By using transfected mutant and wild type receptors, as well as endogenous receptors, we provide pharmacological, biochemical, and physical evidence, based on fluorescence resonance energy transfer analysis, that activation by ligand induces SSTR dimerization, both homo- and heterodimerization with other members of the SSTR family, and that dimerization alters the functional properties of the receptor such as ligand binding affinity and agonist-induced receptor internalization and up-regulation. Double label confocal fluorescence microscopy showed that when SSTR1 and SSTR5 subtypes were coexpressed in Chinese hamster ovary-K1 cells and treated with agonist they underwent internalization and were colocalized in cytoplasmic vesicles. SSTR5 formed heterodimers with SSTR1 but not with SSTR4 suggesting that heterodimerization is a specific process that is restricted to some but not all receptor subtype combinations. Direct protein interaction between different members of the SSTR subfamily defines a new level of molecular cross-talk between subtypes of the SSTR and possibly related receptor families.
Topics: Dimerization; Energy Transfer; Fluorescence; Humans; Membrane Proteins; Peptide Fragments; Protein Conformation; Receptors, Somatostatin; Recombinant Proteins; Somatostatin
PubMed: 10713101
DOI: 10.1074/jbc.275.11.7862 -
Hellenic Journal of Nuclear Medicine 2023Theranostics is an emerging field in medicine that combines diagnostics and therapeutics into a single approach. Overall, theranostics represents a promising paradigm...
Theranostics is an emerging field in medicine that combines diagnostics and therapeutics into a single approach. Overall, theranostics represents a promising paradigm for personalized medicine, as it allows for targeted and precise treatment based on individual patient characteristics. In nuclear medicine, theranostics involves the use of radiopharmaceuticals that have both diagnostic and therapeutic properties. Moreover, theranostics in nuclear medicine offers several advantages over traditional cancer treatments. Unlike radiotherapy, in nuclear medicine the therapy is systemic that targets both primary tumors and metastatic lesions, offering a more comprehensive treatment approach. Additionally, nuclear medicine therapy has been shown to have fewer side effects compared to traditional chemotherapy, making it a more tolerable treatment option for patients. While theranostics in nuclear medicine is still a relatively new field, it has shown promising results in the treatment of neuroendocrine tumors (NETs). One example of a theranostic approach in nuclear medicine is the use of radiolabeled somatostatin analogs for the treatment of NETs. Somatostatin is a hormone that regulates the release of other hormones in the body. It also binds to somatostatin receptors, which are highly expressed in NETs. The first step in theranostics for NETs is the diagnosis and staging of the disease using a radiolabeled somatostatin analog and PET/CT imaging. This allows for the detection of the tumor and assessment of its size and location. Once the tumor has been identified, the same radiolabeled somatostatin analog can be used as a therapeutic agent. The radiopharmaceutical delivers radiation directly to the tumor cells, which destroys them while sparing surrounding healthy tissue. This is known as peptide receptor radionuclide therapy (PRRT). The use of theranostics in NETs also involves the identification of specific somatostatin receptor subtypes that are expressed in the tumor cells. This is important as different somatostatin analogs have varying affinities for different receptor subtypes. By selecting the appropriate radiolabeled somatostatin analog, clinicians can increase the specificity of the therapy, delivering radiation to the tumor cells while minimizing damage to healthy tissue. PRRT has been shown to be effective in treating NETs, particularly those that are resistant to other forms of treatment. It can also be used in combination with other therapies, such as chemotherapy and surgery, to improve outcomes. As research continues, it is likely that theranostics in nuclear medicine will become an increasingly important tool in the fight against cancer, particularly in the context of NETs, offering personalized, targeted treatment options that improve patient outcomes.
Topics: Humans; Precision Medicine; Positron Emission Tomography Computed Tomography; Nuclear Medicine; Somatostatin; Radionuclide Imaging; Neuroendocrine Tumors; Receptors, Somatostatin; Radiopharmaceuticals
PubMed: 37658562
DOI: No ID Found -
The Yale Journal of Biology and Medicine 1997Somatostatin receptors are present in the normal adrenal cortex and medulla. These receptors are also expressed by tumors that cause Cushing's syndrome and by... (Review)
Review
Somatostatin receptors are present in the normal adrenal cortex and medulla. These receptors are also expressed by tumors that cause Cushing's syndrome and by pheochromocytomas. Somatostatin analogues such as octreotide have been developed to target somatostatin receptors for diagnostic and therapeutic purposes. This article reviews the current knowledge of the biology of somatostatin receptors in the normal adrenal gland and in adrenal tumors and defines the current role of the somatostatin receptor in the diagnosis, staging and management of Cushing's syndrome and pheochromocytomas.
Topics: Adrenal Gland Neoplasms; Adrenocorticotropic Hormone; Animals; Cushing Syndrome; Forecasting; Humans; Pheochromocytoma; Radionuclide Imaging; Receptors, Somatostatin; Sensitivity and Specificity
PubMed: 9825485
DOI: No ID Found