Somatostatin receptors: news in the pituitary, lessons for the periphery

2017 ◽  
Author(s):  
Justo Pastor Castano
Keyword(s):  
Somatostatin Receptors

scholarly journals Chemotherapy-Induced Upregulation of Somatostatin Receptor-2 Increases the Uptake and Efficacy of 177Lu-DOTA-Octreotate in Neuroendocrine Tumor Cells

Cancers ◽  
2021 ◽  
Vol 13 (2) ◽  
pp. 232
Author(s):  
Rashmi G. Shah ◽  
Marine A. Merlin ◽  
Samuel Adant ◽  
Fayçal Zine-Eddine ◽  
Jean-Mathieu Beauregard ◽  
...  
Keyword(s):  
Somatostatin Receptor ◽  
Somatostatin Receptors ◽  
Objective Response ◽  
Peptide Receptor Radionuclide Therapy ◽  
Normal Cells ◽  
Radiation Delivery ◽  
Different Types ◽  
Pre Treatment ◽  
High Doses ◽  
Low Dose Chemotherapy

The peptide receptor radionuclide therapy (PRRT) with 177Lu-DOTA-octreotate (LuTate) is recommended for different types of neuroendocrine tumors (NETs) which overexpress somatostatin receptors (SSTR). A combination with chemotherapy improves objective response to LuTate in NET patients and here we characterized chemotherapy-induced upregulation of SSTR2 receptors as a cause for this improved response to LuTate. The NET cell lines with low (BON-1) or relatively high (NCI-H727) SSTR2-expression levels, and non-NET cancer and normal cells were treated with chemotherapeutic drugs and assessed for upregulation of SSTR2. We report that an exposure to low or high doses of drugs, such as temozolomide for 24 h or 5 day results in upregulation of SSTR2 between 3–7 days, increased LuTate uptake and decreased rate of cell proliferation. This effect is at the level of SSTR2-mRNA and is more pronounced in low SSTR2 expressing BON-1 than in high SSTR2 expressing NCI-H727 or non-NET cancer or normal cells. Thus, a properly timed pre-treatment with low-dose chemotherapy could not only improve therapeutic efficacy of LuTate in NET patients who are presently eligible for PRRT, but also allow PRRT to be administered to patients with low SSTR-expressing NETs, who would otherwise not respond to this modality because of insufficient radiation delivery.

scholarly journals Distinct Subsets of Somatostatin Receptors on Cultured Human Lymphocytes

1989 ◽  
Vol 264 (2) ◽  
pp. 949-952
Author(s):  
S P Sreedharan ◽  
K T Kodama ◽  
K E Peterson ◽  
E J Goetzl
Keyword(s):  
Human Lymphocytes ◽  
Somatostatin Receptors

scholarly journals Subtype-specific signaling mechanisms of somatostatin receptors SSTR1 and SSTR2.

1994 ◽  
Vol 269 (14) ◽  
pp. 10357-10362
Author(s):  
C. Hou ◽  
R.L. Gilbert ◽  
D.L. Barber
Keyword(s):  
Somatostatin Receptors ◽  
Signaling Mechanisms

scholarly journals Selection of the First 99mTc-Labelled Somatostatin Receptor Subtype 2 Antagonist for Clinical Translation—Preclinical Assessment of Two Optimized Candidates

2020 ◽  
Vol 14 (1) ◽  
pp. 19
Author(s):  
Melpomeni Fani ◽  
Viktoria Weingaertner ◽  
Petra Kolenc Peitl ◽  
Rosalba Mansi ◽  
Raghuvir H. Gaonkar ◽  
...  
Keyword(s):  
Protein Binding ◽  
Somatostatin Receptor ◽  
Somatostatin Receptors ◽  
Preclinical Study ◽  
Clinical Translation ◽  
Hek293 Cells ◽  
Neuroendocrine Neoplasms ◽  
Receptor Subtype ◽  
Selection Of

Recently, radiolabelled antagonists targeting somatostatin receptors subtype 2 (SST2) in neuroendocrine neoplasms demonstrated certain superior properties over agonists. Within the ERA-PerMED project “TECANT” two 99mTc-Tetramine (N4)-derivatized SST2 antagonists (TECANT-1 and TECANT-2) were studied for the selection of the best candidate for clinical translation. Receptor-affinity, internalization and dissociation studies were performed in human embryonic kidney-293 (HEK293) cells transfected with the human SST2 (HEK-SST2). Log D, protein binding and stability in human serum were assessed. Biodistribution and SPECT/CT studies were carried out in nude mice bearing HEK-SST2 xenografts, together with dosimetric estimations from mouse-to-man. [99mTc]Tc-TECANT-1 showed higher hydrophilicity and lower protein binding than [99mTc]-TECANT-2, while stability was comparable. Both radiotracers revealed similar binding affinity, while [99mTc]Tc-TECANT-1 had higher cellular uptake (>50%, at 2 h/37 °C) and lower dissociation rate (<30%, at 2 h/37 °C). In vivo, [99mTc]Tc-TECANT-1 showed lower blood values, kidney and muscles uptake, whereas tumour uptake was comparable to [99mTc]Tc-TECANT-2. SPECT/CT imaging confirmed the biodistribution results, providing the best tumour-to-background image contrast for [99mTc]Tc-TECANT-1 at 4 h post-injection (p.i.). The estimated radiation dose amounted to approximately 6 µSv/MBq for both radiotracers. This preclinical study provided the basis of selection of [99mTc]Tc-TECANT-1 for clinical translation of the first 99mTc-based SST2 antagonist.

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