Detection of naturally expressed receptors for gastrin-releasing peptide and tachykinins using cyanine 3-labelled neuropeptides

1996 ◽  
Vol 28 (11) ◽  
pp. 811-826 ◽  
Author(s):  
Nigel W. Bunnett ◽  
Donald G. Payan ◽  
Eileen F. Grady
Keyword(s):  
Gastrin Releasing Peptide

Wertigkeit des Pro-Gastrin releasing peptide (Pro-GRP) zur Diagnostik und Therapiekontrolle beim kleinzelligen Bronchialcarcinom

Pneumologie ◽  
2004 ◽  
Vol 58 (S 1) ◽  
Author(s):  
S Krüger ◽  
E Dankelmann ◽  
J v Pawel ◽  
T Duell ◽  
K Häußinger
Keyword(s):  
Gastrin Releasing Peptide

scholarly journals Serines and threonines in the gastrin-releasing peptide receptor carboxyl terminus mediate internalization.

1993 ◽  
Vol 268 (27) ◽  
pp. 20285-20290
Author(s):  
R.V. Benya ◽  
Z Fathi ◽  
J.F. Battey ◽  
R.T. Jensen
Keyword(s):  
Carboxyl Terminus ◽  
Peptide Receptor ◽  
Gastrin Releasing Peptide

scholarly journals 68Ga-Radiolabeling and Pharmacological Characterization of a Kit-Based Formulation of the Gastrin-Releasing Peptide Receptor (GRP-R) Antagonist RM2 for Convenient Preparation of [68Ga]Ga-RM2

Pharmaceutics ◽  
2021 ◽  
Vol 13 (8) ◽  
pp. 1160
Author(s):  
Adrien Chastel ◽  
Delphine Vimont ◽  
Stephane Claverol ◽  
Marion Zerna ◽  
Sacha Bodin ◽  
...  
Keyword(s):  
Calcium Mobilization ◽  
Pharmacological Characterization ◽  
Peptide Receptor ◽  
Gastrin Releasing Peptide ◽  
Production Route ◽  
Membrane Bound ◽  
One Year ◽  
Calcium Mobilization Assay

Background: [68Ga]Ga-RM2 is a potent Gastrin-Releasing Peptide-receptor (GRP-R) antagonist for imaging prostate cancer and breast cancer, currently under clinical evaluation in several specialized centers around the world. Targeted radionuclide therapy of GRP-R-expressing tumors is also being investigated. We here report the characteristics of a kit-based formulation of RM2 that should ease the development of GRP-R imaging and make it available to more institutions and patients. Methods: Stability of the investigated kits over one year was determined using LC/MS/MS and UV-HPLC. Direct 68Ga-radiolabeling was optimized with respect to buffer (pH), temperature, reaction time and shaking time. Conventionally prepared [68Ga]Ga-RM2 using an automated synthesizer was used as a comparator. Finally, the [68Ga]Ga-RM2 product was assessed with regards to hydrophilicity, affinity, internalization, membrane bound fraction, calcium mobilization assay and efflux, which is a valuable addition to the in vivo literature. Results: The kit-based formulation, kept between 2 °C and 8 °C, was stable for over one year. Using acetate buffer pH 3.0 in 2.5–5.1 mL total volume, heating at 100 °C during 10 min and cooling down for 5 min, the [68Ga]Ga-RM2 produced by kit complies with the requirements of the European Pharmacopoeia. Compared with the module production route, the [68Ga]Ga-RM2 produced by kit was faster, displayed higher yields, higher volumetric activity and was devoid of ethanol. In in vitro evaluations, the [68Ga]Ga-RM2 displayed sub-nanomolar affinity (Kd = 0.25 ± 0.19 nM), receptor specific and time dependent membrane-bound fraction of 42.0 ± 5.1% at 60 min and GRP-R mediated internalization of 24.4 ± 4.3% at 30 min. The [natGa]Ga-RM2 was ineffective in stimulating intracellular calcium mobilization. Finally, the efflux of the internalized activity was 64.3 ± 6.5% at 5 min. Conclusion: The kit-based formulation of RM2 is suitable to disseminate GRP-R imaging and therapy to distant hospitals without complex radiochemistry equipment.

scholarly journals In Vivo Biodistribution and Efficacy Evaluation of NeoB, a Radiotracer Targeted to GRPR, in Mice Bearing Gastrointestinal Stromal Tumor

Cancers ◽  
2021 ◽  
Vol 13 (5) ◽  
pp. 1051
Author(s):  
Christopher Montemagno ◽  
Florian Raes ◽  
Mitra Ahmadi ◽  
Sandrine Bacot ◽  
Marlène Debiossat ◽  
...  
Keyword(s):  
Therapeutic Agent ◽  
Tumor Volume ◽  
Tumor Regression ◽  
Efficacy Evaluation ◽  
Peptide Receptor ◽  
Gastrin Releasing Peptide ◽  
Target Organs ◽  
G Protein Coupled ◽  
Complete Tumor

NeoB is a radiotracer targeting the gastrin-releasing peptide receptor (GRPR), a G-protein–coupled receptor expressed in various cancers. The aim of the present study was to evaluate the biodistribution and efficacy of this new therapeutic agent in Gastrointestinal Stromal Tumors (GIST). Eighty-two SCID mice bearing GIST-882 tumors were employed. [177Lu]Lu-NeoB biodistribution was evaluated up to seven days by organ sampling (200 pmol/0.8 MBq, i.v.). For efficacy evaluation, mice received either saline, 400 pmol or 800 pmol of [177Lu]Lu-NeoB (37MBq, 1/w, 3 w, i.v.). SPECT/CT imaging was performed at 24 h, and tumor volume was determined up to 100 days. Elevated and specific [177Lu]Lu-NeoB uptake was found in the GIST tumor, as demonstrated by in vivo competition (19.1 ± 3.9 %ID/g vs. 0.3 ± 0.1 %ID/g at 4h). [177Lu]Lu-NeoB tumor retention (half-life of 40.2 h) resulted in elevated tumor-to-background ratios. Tumor volumes were significantly reduced in both treated groups (p < 0.01), even leading to complete tumor regression at the 400 pmol dose. [177Lu]Lu-NeoB exhibited excellent pharmacokinetics with elevated and prolonged tumor uptake and low uptake in non-target organs such as pancreas. The potential of this new theragnostic agent in different indications, including GIST, is under evaluation in the FIH [177Lu]Lu-NeoB clinical trial.

scholarly journals Development of bispecific theranostic ligand targeting the prostate specific membrane antigen (PSMA) and gastrin releasing peptide (GRPR) receptor

2021 ◽  
Vol 96-97 ◽  
pp. S29-S30
Author(s):  
Danai Bouzioti ◽  
Martin Schaefer ◽  
Ulrike Bauder-Wuest ◽  
Barbara Mavroidi ◽  
Evangelos Machairas ◽  
...  
Keyword(s):  
Prostate Specific Membrane Antigen ◽  
Gastrin Releasing Peptide ◽  
Specific Membrane
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