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Pituitary Feb 2017First-generation somatostatin receptors ligands (SRL) are the mainstay in the medical treatment of acromegaly, however the percentage of patients controlled with these... (Review)
Review
First-generation somatostatin receptors ligands (SRL) are the mainstay in the medical treatment of acromegaly, however the percentage of patients controlled with these drugs significantly varies in the different studies. Many factors are involved in the resistance to SRL. In this review, we update the physiology of somatostatin and its receptors (sst), the use of SRL in the treatment of acromegaly and the factors involved in the response to these drugs. The SRL act through interaction with the sst, which up to now have been characterized as five subtypes. The first-generation SRL, octreotide and lanreotide, are considered sst2 specific and have biochemical response rates varying from 20 to 70%. Tumor volume reduction can be found in 36-75% of patients. Several factors may determine the response to these drugs, such as sst, AIP, E-cadherin, ZAC1, filamin A and β-arrestin expression in the somatotropinomas. In patients resistant to first-generation SRL, alternative medical treatment options include: SRL high dose regimens, SRL in combination with cabergoline or pegvisomant, or the use of pasireotide. Pasireotide is a next-generation SRL with a broader pattern of interaction with sst. In the light of the recent increase of treatment options in acromegaly and the deeper knowledge of the determinants of response to the current first-line therapy, a shift from a trial-and-error treatment to a personalized one could be possible.
Topics: Acromegaly; Humans; Octreotide; Peptides, Cyclic; Receptors, Somatostatin; Somatostatin
PubMed: 28176162
DOI: 10.1007/s11102-017-0791-0 -
Best Practice & Research. Clinical... Sep 2023Neuroendocrine neoplasms are rare and heterogenous group of tumors with varying degrees of clinical presentations and involvement of multiple organ systems in the body.... (Review)
Review
Neuroendocrine neoplasms are rare and heterogenous group of tumors with varying degrees of clinical presentations and involvement of multiple organ systems in the body. In the modern clinical practice somatostatin receptor molecular imaging and targeted radioligand therapy plays a vital role in the diagnosis and management of the disease. Several new and promising radiotracers for NET imaging and theranostics, belonging to various groups and classes are being studied and investigated. This exponential growth of radiotracers poses concerns about the indication, clinical benefit, and safety profile of the agents. We discuss the basis behind these radiotracers clinical use, receptor targeting and intra and inter tumor heterogeneity. Furthermore, role of dual tracer imaging, combination therapy and potential applications of dosimetry in predicting treatment outcome and safety profile is reviewed. Individualized precision medicine with better tumor characterization, maximum therapeutic benefit and minimum toxicity is the way forward for future medicine.
Topics: Humans; Neuroendocrine Tumors; Radiopharmaceuticals; Positron-Emission Tomography; Positron Emission Tomography Computed Tomography; Receptors, Somatostatin
PubMed: 37468403
DOI: 10.1016/j.beem.2023.101797 -
Revista Espanola de Medicina Nuclear E... 2022This continuing education aims to present in a clear and easy-to-understand way, the biology of neuroendocrine tumors (NETs), the characteristics of somatostatin...
This continuing education aims to present in a clear and easy-to-understand way, the biology of neuroendocrine tumors (NETs), the characteristics of somatostatin receptors, the selection of patients for radiolabelled peptide therapy (PRRT), the inclusion criteria to benefit from treatment with the minimum possible adverse effects, the administration protocol, follow-up and response evaluation. The functional imaging studies necessary to explore the biology of the tumor and to individualize the treatment are also carried out, and constitute the cornerstone for the development of teragnosis. Clinical trials are being developed to better define the position of PRRT within the broad therapeutic options, and among the future perspectives, there are several lines of research to improve the objective response rate and survival with PRRT, focused on the development of new agonists and somatostatin receptor antagonists, new radionuclides and radiosensitizing combination therapies. In conclusion, PRRT is a great therapeutic, well-tolerated and safe tool with generally mild and self-limited acute side effects, that must be sequenced at the best moment of the evolution of the disease of patients with NET. Candidate patients for PRRT should always be evaluated by a multidisciplinary clinical committee.
Topics: Heterocyclic Compounds, 1-Ring; Humans; Neuroendocrine Tumors; Radioisotopes; Receptors, Somatostatin
PubMed: 34920969
DOI: 10.1016/j.remnie.2021.11.001 -
Nuclear Medicine and Biology Sep 2016Imaging and therapy using radiolabelled somatostatin analogues are methods successfully used in patients with somatostatin receptor (SSTR)-expressing neuroendocrine... (Review)
Review
Imaging and therapy using radiolabelled somatostatin analogues are methods successfully used in patients with somatostatin receptor (SSTR)-expressing neuroendocrine tumours. Since these techniques were first introduced, many improvements have been made. SSTR expression has also been reported on breast cancer (BC). Currently mammography, magnetic resonance imaging and ultrasound are the most frequent methods used for BC imaging. Since SSTR expression on BC was demonstrated, clinical studies examining the feasibility of visualizing primary BC using SSTR radioligands have been performed. However, to date SSTR-mediated nuclear imaging is not used clinically in BC patients. The aim of this review is to assess whether recent improvements made within nuclear medicine may enable SSTR-mediated imaging to play a role in BC management. For this we critically analysed results of past studies and discussed the potential of the improvements made within nuclear medicine on SSTR-mediated nuclear imaging of BC. Seven databases were searched for publications on BC imaging with SSTR radioligands. The papers found were analysed by 3 individual observers to identify whether the studies met the pre-set inclusion criteria defined as studies in which nuclear imaging using radiolabelled SST analogues was performed in patients with breast lesions. Twenty-four papers were selected for this review including studies on SSTR-mediated nuclear imaging in BC, neuroendocrine BC and other breast lesions. The analysed studies were heterogeneous with respect to the imaging method, imaging protocol, patient groups and the radiolabelled SST analogues used. Despite the fact that the analysed studies were heterogeneous, sensitivity for primary BC ranged from 36-100%. In a subset of the studies LN lesions were visualized, but sensitivity was lower compared to that for primary tumours. A part of the studies included benign lesions and specificity ranged from 22-100%. Furthermore, false negatives and false positives were reported. In the majority of the studies scan outcome was not associated with BC subtype.
Topics: Breast Neoplasms; Diagnostic Imaging; Humans; Isotope Labeling; Receptors, Somatostatin; Somatostatin
PubMed: 27409729
DOI: 10.1016/j.nucmedbio.2016.05.012 -
Journal of Nuclear Medicine : Official... Mar 2024Most well-differentiated neuroendocrine tumors (NETs) express high levels of somatostatin receptors, particularly subtypes 2 and 5. Somatostatin analogs (SSAs) bind to...
Most well-differentiated neuroendocrine tumors (NETs) express high levels of somatostatin receptors, particularly subtypes 2 and 5. Somatostatin analogs (SSAs) bind to somatostatin receptors and are used for palliation of hormonal syndromes and control of tumor growth. The long-acting SSAs octreotide long-acting release and lanreotide are commonly used in the first-line metastatic setting because of their tolerable side effect profile. Radiolabeled SSAs are used both for imaging and for treatment of NETs. Lu-DOTATATE is a β-emitting radiolabeled SSA that has been proven to significantly improve progression-free survival among patients with progressive midgut NETs and is approved for treatment of metastatic gastroenteropancreatic NETs. A key question in management of patients with gastroenteropancreatic and lung NETs is the sequencing of Lu-DOTATATE in relation to other systemic treatments (such as everolimus) or liver-directed therapies. This question is particularly complicated given the heterogeneity of NETs and the near absence of randomized trials comparing active treatment options. This state-of-the-art review examines the evidence supporting use of somatostatin-receptor-targeted treatments within the larger landscape of NET therapy and offers insights regarding optimal patient selection, assessment of benefit versus risk, and treatment sequencing.
Topics: Humans; Neuroendocrine Tumors; Receptors, Somatostatin; Carcinoma, Neuroendocrine; Somatostatin; Octreotide; Neoplasms, Second Primary
PubMed: 38238038
DOI: 10.2967/jnumed.123.265706 -
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 -
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 -
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