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European Journal of Nuclear Medicine... Oct 2019
Topics: Fluorine Radioisotopes; Heterocyclic Compounds, 1-Ring; Octreotide; Receptors, Somatostatin
PubMed: 31392370
DOI: 10.1007/s00259-019-04474-6 -
Journal of Nuclear Medicine : Official... Dec 2023Somatostatin receptor (SSTR) expression in metastatic lung neuroendocrine tumors (NETs) has not been well characterized using PET imaging. Understanding the degree and...
Somatostatin receptor (SSTR) expression in metastatic lung neuroendocrine tumors (NETs) has not been well characterized using PET imaging. Understanding the degree and uniformity of SSTR expression is important to establish the role of SSTR-targeted treatments in lung NETs. A retrospective institutional review of patients with metastatic lung NETs who underwent DOTATATE PET imaging from March 2017 to February 2023 was performed. In total, 48 patients with metastatic lung NETs who underwent Ga- or Cu-DOTATATE PET imaging were identified. Four had completely negative SSTR expression, and 10 had very weak expression (less than in a normal liver). Among the remaining 34 patients, 21 had uniformly positive DOTATATE PET scans, and 13 had heterogeneous expression. Only 44% had uniformly positive receptor expression, identifying them as candidates for peptide receptor radionuclide therapy. Most metastatic lung NETs lack uniform SSTR expression and are thus suboptimal candidates for SSTR-targeted therapy. SSTR imaging in lung NETs should be evaluated carefully for uniformity of expression.
Topics: Humans; Receptors, Somatostatin; Neuroendocrine Tumors; Retrospective Studies; Positron-Emission Tomography; Carcinoma, Neuroendocrine; Lung; Organometallic Compounds; Positron Emission Tomography Computed Tomography
PubMed: 37797976
DOI: 10.2967/jnumed.123.266185 -
Pathology International Oct 2021Prostatic and colon carcinomas with neuroendocrine differentiation are reported to behave more aggressively than those without such differentiation. In hepatocellular...
Prostatic and colon carcinomas with neuroendocrine differentiation are reported to behave more aggressively than those without such differentiation. In hepatocellular carcinomas (HCCs), however, only a few studies have reported the expression status of neuroendocrine markers and somatostatin receptor 2, the main target of a somatostatin analog. Furthermore, the prognostic significance of the markers in HCCs has not been fully explored. We evaluated the expression of the neuroendocrine makers (chromogranin A, synaptophysin, and CD56) and somatostatin receptor 2 (SSTR2) in 95 HCCs, and investigated the correlation between the expression of these markers and clinicopathological findings. Chromogranin A was immunolocalized in 2 cases, synaptophysin in 15 cases, CD56 in 11 cases, and SSTR2 in 19 cases. Immunoreactivity of synaptophysin and CD56 were the significant unfavorable prognostic factors in terms of 2-year disease-free survival (DFS) and the overall survival (OS) along with a high nuclear mitosis level (>10/10 high-power field), a larger tumor size (>5 cm), the presence of vascular and/or biliary invasion, and high TNM stage (III/IV). Multivariate Cox proportional hazards analysis identified synaptophysin as an independent prognostic factor for 2-year DFS and OS. Synaptophysin expression can be used to predict an unfavorable prognosis in patients with HCC.
Topics: Adult; Aged; Aged, 80 and over; Biomarkers, Tumor; CD56 Antigen; Carcinoma, Hepatocellular; Chromogranin A; Female; Humans; Liver Neoplasms; Male; Middle Aged; Prognosis; Receptors, Somatostatin; Retrospective Studies; Survival Analysis; Synaptophysin
PubMed: 34320691
DOI: 10.1111/pin.13149 -
Hormone and Metabolic Research =... Jan 2020Pituitary adenomas represent approximately 15% of brain tumors; incidence is significantly on the increase due to widespread use of magnetic resonance imaging. Surgery... (Review)
Review
Pituitary adenomas represent approximately 15% of brain tumors; incidence is significantly on the increase due to widespread use of magnetic resonance imaging. Surgery remains the first-line treatment for most tumors overall. The role of dopaminergic agonists (DAs) and somatostatin receptor ligands (SRLs) in the treatment of pituitary adenomas is quite well established for prolactinomas and growth hormone (GH) excess. However, over the last decade new multi-receptor binding SRLs are increasingly used for treatment of acromegaly and Cushing's disease. SRLs/DA chimeric compounds seem to have enhanced potency and efficacy when compared to that of individual SRLs or DA receptor agonists according to preclinical data. However, following negative results, more research is needed to determine if this interesting mechanism will translate into positive clinical effects for acromegaly patients. Furthermore, new agents that block adrenal steroidogenesis have been developed in phase III clinical trials for Cushing's disease and several new compounds working at the pituitary level and/or blocking the glucocorticoid receptor are also in development. Combination therapy of drugs with similar or different mechanisms (possibly synergistic) are also on the increase. A growing awareness regarding all mechanisms involved in both control of pituitary secretion and cellular proliferation might allow for sole medical treatment of pituitary adenomas, especially macroadenomas, rather than surgery and/or radiation therapy, in the future. Moreover, the underlying decision on how to treat patients with pituitary adenomas should be individualized on a case-by-case basis with not only a goal of tumor shrinkage and biochemical control, but also of improving patients' quality of life.
Topics: Animals; Clinical Trials as Topic; Dopamine Agonists; Humans; Pituitary ACTH Hypersecretion; Pituitary Neoplasms; Receptors, Somatostatin
PubMed: 31863423
DOI: 10.1055/a-1066-4592 -
Endocrine Oct 2020Propylthiouracil (PTU)-induced hypothyroidism is a well-established model for assessing hormonal and morphological changes in thyroid as well as other central and...
PURPOSE
Propylthiouracil (PTU)-induced hypothyroidism is a well-established model for assessing hormonal and morphological changes in thyroid as well as other central and peripheral tissues. Somatostatin (SST) is known to regulate hormonal secretion and synthesis in endocrine tissues; however, nothing is currently known about the distribution of SST and its receptor in hypothyroidism.
METHOD
In the present study, the comparative immunohistochemical distribution of SST and somatostatin receptors (SSTRs) were analyzed in PTU-induced hypothyroid rats. Rats were treated with PTU for 15 days followed by a co-administration of levothyroxine (LVT) for 15 days. After PTU and LVT treatments (day 30), rats were further administered LVT alone for 15 more days (day 45). The subcellular distribution of SST and SSTR subtypes was determined by peroxidase immunohistochemistry in the thyroid gland collected from control and treated rats.
RESULTS
SST and SSTR subtypes were found to be moderately expressed in control thyroid tissues. SST and SSTR subtypes like immunoreactivity increased significantly in follicular and parafollicular epithelial cells in the thyroid of PTU-treated rats. The PTU-induced changes in the expression of SST and SSTR subtypes were suppressed by the administration of the LVT. In addition to thyroid tissues, SST and SSTRs expression was also changed in non-follicular tissues including blood vessels, smooth muscle cells, and connective tissue following treatments.
CONCLUSION
The present study revealed a distinct subcellular distribution of SST and SSTR subtypes in the thyroid and provides a new insight for the role of SST and SSTR subtypes in hypothyroidism in addition to its well-established role in negative regulation of hormonal secretion.
Topics: Animals; Hypothyroidism; Propylthiouracil; Rats; Receptors, Somatostatin; Somatostatin
PubMed: 32335798
DOI: 10.1007/s12020-020-02309-1 -
Journal of Neuroendocrinology Jun 2022For patients with gastroenteropancreatic neuroendocrine tumours (GEP-NET), health-related quality of life (HRQoL) is important. Meanwhile, whether tumour volume is...
For patients with gastroenteropancreatic neuroendocrine tumours (GEP-NET), health-related quality of life (HRQoL) is important. Meanwhile, whether tumour volume is associated with HRQoL is unknown. Hence, the aim of this study was to assess if total somatostatin receptor expressing tumour volume is correlated with HRQoL in patients with metastatic GEP-NET. Some 71 patients were included in the study. HRQoL and NET-specific symptoms were assessed with EORTC QLQ-C30 and EORTC GI.NET21. A summary score was calculated from the output of the QLQ-C30. Total somatostatin receptor expressing tumour volume was retrospectively evaluated on somatostatin receptor imaging with positron emission tomography-computed tomography ( Ga-DOTA-TATE/TOC PET-CT) in each patient. Simple and multiple linear regression were used to evaluate the correlation between tumour volume and HRQoL, controlling for potential confounders. No correlation was found between total somatostatin receptor expressing tumour volume and QLQ-C30 summary score. Weak positive correlations were found between total tumour volume and the specific symptoms dyspnoea, diarrhoea and flushing. To the best of our knowledge, this is the first study to evaluate the association between total somatostatin expressing tumour volume and HRQoL. Our results indicate that, while tumour volume is weakly associated with symptom severity of the carcinoid syndrome, other factors might impact more on overall HRQoL.
Topics: Humans; Neuroendocrine Tumors; Positron Emission Tomography Computed Tomography; Quality of Life; Receptors, Somatostatin; Retrospective Studies; Tumor Burden
PubMed: 35488399
DOI: 10.1111/jne.13139 -
Diabetes, Obesity & Metabolism May 2022To evaluate the pharmacokinetics and efficacy of a novel somatostatin receptor 2 antagonist, ZT-01, to stimulate glucagon release in rats with type 1 diabetes (T1D).
AIM
To evaluate the pharmacokinetics and efficacy of a novel somatostatin receptor 2 antagonist, ZT-01, to stimulate glucagon release in rats with type 1 diabetes (T1D).
METHODS
The pharmacokinetics of ZT-01 and PRL-2903 were assessed following intraperitoneal or subcutaneous dosing at 10 mg/kg. We compared the efficacy of ZT-01 with PRL-2903 to prevent hypoglycaemia during an insulin bolus challenge and under hypoglycaemic clamp conditions.
RESULTS
Within 1 hour after intraperitoneal administration, ZT-01 achieved more than 10-fold higher plasma Cmax compared with PRL-2903. Twenty-four hour exposure was 4.7× and 11.3× higher with ZT-01 by the intraperitoneal and subcutaneous routes, respectively. The median time to reach hypoglycaemia of more than 3.0 mmol/L was 60, 70, and 125 minutes following vehicle, PRL-2903, or ZT-01 administration, respectively. Furthermore, rats receiving ZT-01 had significantly higher glucose nadirs following insulin administration compared with PRL-2903- and vehicle-treated rats. During the hypoglycaemic clamp, ZT-01 increased peak glucagon responses by ~4-fold over PRL-2903.
CONCLUSIONS
We conclude that ZT-01 may be effective in restoring glucagon responses and preventing the onset of hypoglycaemia in patients with T1D.
Topics: Animals; Blood Glucose; Diabetes Mellitus, Type 1; Glucagon; Humans; Hypoglycemia; Insulin; Rats; Receptors, Somatostatin
PubMed: 35060297
DOI: 10.1111/dom.14652 -
AJR. American Journal of Roentgenology May 2022Neuroendocrine neoplasms (NENs) encompass a broad spectrum of tumors throughout the body and range in biologic behavior from indolent to aggressive. Consequently, a wide... (Review)
Review
Neuroendocrine neoplasms (NENs) encompass a broad spectrum of tumors throughout the body and range in biologic behavior from indolent to aggressive. Consequently, a wide spectrum of treatment options are available for NENs, including observation, somatostatin analogues, targeted therapy, chemotherapy, surgical resection, liver-directed therapy (embolization and ablation), and peptide receptor radionuclide therapy. Given the wide variety of tumor behaviors and treatments, precise criteria for treatment response in NENs are lacking. Though conventional anatomic imaging with CT and MRI remains important for NEN response assessment, the use of somatostatin receptor (SSR) PET is increasing and often provides synergistic and complementary information. Additionally, in certain clinical scenarios, a particular imaging strategy may prove superior or inferior to others for the detection of metastatic disease and evaluation of therapy response. A strong need exists to further define appropriate and standardized assessment criteria for tumor response and progression in NEN. This article presents the strengths and weaknesses of individual imaging modalities for evaluating NEN therapy response, including conventional anatomic imaging, SSR PET, FDG PET, dual-tracer PET, and PET/MRI. Ongoing challenges and unmet needs in the use of imaging for NEN response evaluation are explored.
Topics: Humans; Neuroendocrine Tumors; Positron Emission Tomography Computed Tomography; Positron-Emission Tomography; Receptors, Somatostatin; Somatostatin
PubMed: 34985313
DOI: 10.2214/AJR.21.27159 -
International Journal of Molecular... Aug 2022Acromegaly is a chronic and systemic disease due to excessive growth hormone and insulin-like growth factor type I caused, in the vast majority of cases, by a... (Review)
Review
Acromegaly is a chronic and systemic disease due to excessive growth hormone and insulin-like growth factor type I caused, in the vast majority of cases, by a GH-secreting pituitary adenoma. About 40% of these tumors have somatic mutations in the stimulatory G protein alpha-subunit 1 gene. The pathogenesis of the remaining tumors, however, is still not fully comprehended. Surgery is the first-line therapy for these tumors, and first-generation somatostatin receptor ligands (fg-SRL) are the most prescribed medications in patients who are not cured by surgery. MicroRNAs are small, non-coding RNAs that control the translation of many mRNAs, and are involved in the post-transcriptional regulation of gene expression. Differentially expressed miRNAs can explain differences in the pathogenesis of acromegaly and tumor resistance. In this review, we focus on the most validated miRNAs, which are mainly involved in acromegaly’s tumorigenesis and fg-SRL resistance, as well as in circulating miRNAs in acromegaly.
Topics: Acromegaly; Adenoma; Human Growth Hormone; Humans; Insulin-Like Growth Factor I; MicroRNAs; Receptors, Somatostatin; Somatostatin
PubMed: 35955787
DOI: 10.3390/ijms23158653 -
Molecules (Basel, Switzerland) Sep 2020Identified in 1973, somatostatin (SST) is a cyclic hormone peptide with a short biological half-life. Somatostatin receptors (SSTRs) are widely expressed in the whole... (Review)
Review
Identified in 1973, somatostatin (SST) is a cyclic hormone peptide with a short biological half-life. Somatostatin receptors (SSTRs) are widely expressed in the whole body, with five subtypes described. The interaction between SST and its receptors leads to the internalization of the ligand-receptor complex and triggers different cellular signaling pathways. Interestingly, the expression of SSTRs is significantly enhanced in many solid tumors, especially gastro-entero-pancreatic neuroendocrine tumors (GEP-NET). Thus, somatostatin analogs (SSAs) have been developed to improve the stability of the endogenous ligand and so extend its half-life. Radiolabeled analogs have been developed with several radioelements such as indium-111, technetium-99 m, and recently gallium-68, fluorine-18, and copper-64, to visualize the distribution of receptor overexpression in tumors. Internal metabolic radiotherapy is also used as a therapeutic strategy (e.g., using yttrium-90, lutetium-177, and actinium-225). With some radiopharmaceuticals now used in clinical practice, somatostatin analogs developed for imaging and therapy are an example of the concept of personalized medicine with a theranostic approach. Here, we review the development of these analogs, from the well-established and authorized ones to the most recently developed radiotracers, which have better pharmacokinetic properties and demonstrate increased efficacy and safety, as well as the search for new clinical indications.
Topics: Amino Acid Sequence; Animals; Humans; Neoplasms; Peptides; Radiopharmaceuticals; Receptors, Somatostatin; Somatostatin; Tissue Distribution
PubMed: 32887456
DOI: 10.3390/molecules25174012