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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 -
The Journal of Clinical Endocrinology... Mar 2024Insulinomas are hormone-producing pancreatic neuroendocrine neoplasms with an estimated incidence of 1 to 4 cases per million per year. Extrapancreatic insulinomas are...
Insulinomas are hormone-producing pancreatic neuroendocrine neoplasms with an estimated incidence of 1 to 4 cases per million per year. Extrapancreatic insulinomas are extremely rare. Most insulinomas present with the Whipple triad: (1) symptoms, signs, or both consistent with hypoglycemia; (2) a low plasma glucose measured at the time of the symptoms and signs; and (3) relief of symptoms and signs when the glucose is raised to normal. Nonmetastatic insulinomas are nowadays referred to as "indolent" and metastatic insulinomas as "aggressive." The 5-year survival of patients with an indolent insulinoma has been reported to be 94% to 100%; for patients with an aggressive insulinoma, this amounts to 24% to 67%. Five percent to 10% of insulinomas are associated with the multiple endocrine neoplasia type 1 syndrome. Localization of the insulinoma and exclusion or confirmation of metastatic disease by computed tomography is followed by endoscopic ultrasound or magnetic resonance imaging for indolent, localized insulinomas. Glucagon-like peptide 1 receptor positron emission tomography/computed tomography or positron emission tomography/magnetic resonance imaging is a highly sensitive localization technique for seemingly occult, indolent, localized insulinomas. Supportive measures and somatostatin receptor ligands can be used for to control hypoglycemia. For single solitary insulinomas, curative surgical excision remains the treatment of choice. In aggressive malignant cases, debulking procedures, somatostatin receptor ligands, peptide receptor radionuclide therapy, everolimus, sunitinib, and cytotoxic chemotherapy can be valuable options.
Topics: Humans; Insulinoma; Receptors, Somatostatin; Pancreatic Neoplasms; Hypoglycemia; Neuroendocrine Tumors
PubMed: 37925662
DOI: 10.1210/clinem/dgad641 -
Frontiers in Endocrinology 2021The delay in controlling the disease in patients who do not respond to first-line treatment with first generation somatostatin receptor ligands (first-generation SRLs)... (Review)
Review
The delay in controlling the disease in patients who do not respond to first-line treatment with first generation somatostatin receptor ligands (first-generation SRLs) can be quantified in years, as every modification in the medical therapy requires some months to be fully evaluated. Considering this, acromegaly treatment should benefit from personalized medicine therapeutic approach by using biomarkers identifying drug response. Pasireotide has been positioned mostly as a compound to be used in first-generation SRLs resistant patients and after surgical failure, but sufficient data are now available to indicate it is a first line therapy for patients with certain characteristics. Pasireotide has been proved to be useful in patients in which hyperintensity T2 MRI signal is shown and in those depicting low and high expression of , low or mutated condition and sparsely granulated immunohistochemical pattern. This combination of clinical and pathological characteristics is unique for certain patients and seems to cluster in the same cases, strongly suggesting an etiopathogenic link. Thus, in this paper we propose to include this clinico-pathologic phenotype in the therapeutic algorithm, which would allow us to use as first line medical treatment those compounds with the highest potential for achieving the fastest control of GH hypersecretion as well as a positive effect upon tumor shrinkage, therefore accelerating the implementation of precision medicine for acromegaly. Moreover, we suggest the development, validation and clinical use of a pasireotide acute test, able to identify patients responsive to pasireotide LAR as the acute octreotide test is able to do for SRLs.
Topics: Acromegaly; Adenoma; Algorithms; Biomarkers; Endocrine Gland Neoplasms; Genetic Markers; Growth Hormone-Secreting Pituitary Adenoma; Humans; Image Processing, Computer-Assisted; Insulin-Like Growth Factor I; Ligands; Machine Learning; Magnetic Resonance Imaging; Models, Genetic; Octreotide; Phosphorylation; Precision Medicine; Receptors, Somatostatin; Somatostatin; Treatment Outcome
PubMed: 33796079
DOI: 10.3389/fendo.2021.648411 -
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 -
The Quarterly Journal of Nuclear... Dec 2021In the last few decades, the incidence and prevalence of neuroendocrine tumors has been increasing. The theragnostic approach, that allows the diagnosis and treatment of...
In the last few decades, the incidence and prevalence of neuroendocrine tumors has been increasing. The theragnostic approach, that allows the diagnosis and treatment of different neoplasms with the same ligand, is a typical nuclear medicine tool. Applied for years, is also pivotal in neuroendocrine tumors (NETs) where it has improved the diagnostic accuracy and the therapeutic efficacy with impact on patient's survival. Theragnostic also allows the identification of important prognostic factors such as tumor location and burden, presence of liver metastases and intensity of somatostatin receptors (SSTR) expression to consider in new and possibly combined studies to ameliorate patient's outcome. Moreover, the possibility to evaluate receptor expression even in non-NET malignancies has de facto widened the possible indications for PRRT. We believe that this innovative therapeutic approach will be implemented in next years by radiomics and biological tumors characterization to better address PRRT applications.
Topics: Humans; Neuroendocrine Tumors; Octreotide; Radionuclide Imaging; Receptors, Somatostatin
PubMed: 34881852
DOI: 10.23736/S1824-4785.21.03426-9 -
AJNR. American Journal of Neuroradiology Aug 2023Due to its high sensitivity, somatostatin receptor-PET may detect smaller lesions and more extensive disease than contrast-enhanced MR imaging, while the superior...
BACKGROUND AND PURPOSE
Due to its high sensitivity, somatostatin receptor-PET may detect smaller lesions and more extensive disease than contrast-enhanced MR imaging, while the superior spatial resolution of MR imaging enables lesions to be accurately localized. We compared results of somatostatin receptor-PET/MRI with those of MR imaging alone and assessed the added value of vertex-to-thigh imaging for head and neck neuroendocrine tumors.
MATERIALS AND METHODS
Somatostatin receptor-PET/CT was acquired as limited brain or head and neck imaging, with optional vertex-to-thigh imaging, following administration of CU/GA DOTATATE. Somatostatin receptor-PET was fused with separately acquired contrast-enhanced MR imaging. DOTATATE activity was classified as comparable, more extensive, and/or showing additional lesions compared with MR imaging. Vertex-to-thigh findings were classified as positive or negative for metastatic disease or incidental.
RESULTS
Thirty patients (with 13 meningiomas, 11 paragangliomas, 1 metastatic papillary thyroid carcinoma, 1 middle ear neuroendocrine adenoma, 1 external auditory canal mass, 1 pituitary carcinoma, 1 olfactory neuroblastoma, 1 orbital mass) were imaged. Five had no evidence of somatostatin receptor-positive lesions and were excluded. In 11/25, somatostatin receptor-PET/MRI and MR imaging were comparable. In 7/25, somatostatin receptor-PET/MRI showed more extensive disease, while in 9/25, somatostatin receptor-PET/MRI identified additional lesions. On vertex-to-thigh imaging, 1 of 17 patients was positive for metastatic disease, 8 of 17 were negative, and 8 of 17 demonstrated incidental findings.
CONCLUSIONS
Somatostatin receptor-PET detected additional lesions and more extensive disease than contrast-enhanced MR imaging alone, while vertex-to-thigh imaging showed a low incidence of metastatic disease. Somatostatin receptor-PET/MRI enabled superior anatomic delineation of tumor burden, while any discrepancies were readily addressed. Somatostatin receptor-PET/MRI has the potential to play an important role in presurgical and radiation therapy planning of head and neck neuroendocrine tumors.
Topics: Humans; Positron Emission Tomography Computed Tomography; Receptors, Somatostatin; Neuroendocrine Tumors; Positron-Emission Tomography; Magnetic Resonance Imaging; Meningeal Neoplasms; Nasal Cavity; Nose Neoplasms; Organometallic Compounds
PubMed: 37442593
DOI: 10.3174/ajnr.A7934 -
Basic & Clinical Pharmacology &... Sep 2022Somatostatin and its analogues, known as somatostatin receptor ligands (SRLs), have been reported to attenuate weight gain in some clinical settings. However, their...
Somatostatin and its analogues, known as somatostatin receptor ligands (SRLs), have been reported to attenuate weight gain in some clinical settings. However, their direct effects on preadipocytes are barely investigated. Therefore, this study aimed to evaluate the influence of SRLs on preadipocytes and to further explore the potential mechanisms. Cell Counting Kit-8 assay, Oil Red O staining, triglyceride contents measurements, quantitative polymerase chain reaction (qPCR) and western blot were used to investigate the effects of SRLs on preadipocytes. We found that three SRLs (octreotide, TT232 and pasireotide) inhibited cell viability after 8-48 h but not 4 h. Further western blot results showed that they significantly suppressed activation of PI3K/Akt pathway. Besides, lipid accumulation was also significantly inhibited by these SRLs. Moreover, mRNA levels of some critical adipogenic markers, including Pparg, Cebpa, Fasn, Fabp4, Acaca and Lpl, were downregulated by the treatments of all these SRLs. Consistently, the protein expression of peroxisome proliferator-activated receptor γ (PPARγ), CCAAT/enhancer binding protein α (C/EBPα) and fatty acid synthase (FAS) was also suppressed by SRLs. SRLs inhibit the proliferation and lipogenesis in preadipocytes. Their inhibitory effects on cell proliferation may be mediated by the downregulated PI3K/Akt pathway, and the suppressive actions on lipogenesis may be related to the decreased PPARγ and C/EBPα expression.
Topics: 3T3-L1 Cells; Adipocytes; Animals; CCAAT-Enhancer-Binding Protein-alpha; Cell Differentiation; Cell Proliferation; Ligands; Lipogenesis; Mice; PPAR gamma; Phosphatidylinositol 3-Kinases; Proto-Oncogene Proteins c-akt; Receptors, Somatostatin; Somatostatin
PubMed: 35688794
DOI: 10.1111/bcpt.13762 -
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