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
| dc.rights.license | open | en_US |
| hal.structure.identifier | Institut de Neurosciences cognitives et intégratives d'Aquitaine [INCIA] | |
| dc.contributor.author | CHASTEL, Adrien | |
| hal.structure.identifier | Institut de Neurosciences cognitives et intégratives d'Aquitaine [INCIA] | |
| dc.contributor.author | VIMONT, Delphine | |
| dc.contributor.author | CLAVEROL, Stephane | |
| dc.contributor.author | ZERNA, Marion | |
| dc.contributor.author | BODIN, Sacha | |
| dc.contributor.author | BERNDT, Mathias | |
| dc.contributor.author | CHAIGNEPAIN, Stephane | |
| hal.structure.identifier | Institut de Neurosciences cognitives et intégratives d'Aquitaine [INCIA] | |
| dc.contributor.author | HINDIE, Elif | |
| hal.structure.identifier | Institut de Neurosciences cognitives et intégratives d'Aquitaine [INCIA] | |
| dc.contributor.author | MORGAT, Clement | |
| dc.date.accessioned | 2022-10-07T10:21:48Z | |
| dc.date.available | 2022-10-07T10:21:48Z | |
| dc.date.issued | 2021-07-28 | |
| dc.identifier.issn | 1999-4923 | en_US |
| dc.identifier.uri | oai:crossref.org:10.3390/pharmaceutics13081160 | |
| dc.identifier.uri | https://oskar-bordeaux.fr/handle/20.500.12278/148366 | |
| dc.description.abstractEn | 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. | |
| dc.language.iso | EN | en_US |
| dc.rights | Attribution 3.0 United States | * |
| dc.rights.uri | http://creativecommons.org/licenses/by/3.0/us/ | * |
| dc.source | crossref | |
| dc.subject.en | GRP-R | |
| dc.subject.en | 68Ga | |
| dc.subject.en | PET | |
| dc.subject.en | kit | |
| dc.title.en | 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 | |
| dc.type | Article de revue | en_US |
| dc.identifier.doi | 10.3390/pharmaceutics13081160 | en_US |
| dc.subject.hal | Sciences du Vivant [q-bio]/Neurosciences [q-bio.NC] | en_US |
| dc.identifier.pubmed | 34452121 | en_US |
| bordeaux.journal | Pharmaceutics | en_US |
| bordeaux.volume | 13 | en_US |
| bordeaux.hal.laboratories | Institut de neurosciences cognitives et intégratives d'Aquitaine (INCIA) - UMR 5287 | en_US |
| bordeaux.issue | 8 | en_US |
| bordeaux.institution | Université de Bordeaux | en_US |
| bordeaux.institution | CNRS | en_US |
| bordeaux.peerReviewed | oui | en_US |
| bordeaux.inpress | non | en_US |
| bordeaux.import.source | dissemin | |
| hal.identifier | hal-03805497 | |
| hal.version | 1 | |
| hal.date.transferred | 2022-10-07T10:21:53Z | |
| hal.export | true | |
| workflow.import.source | dissemin | |
| dc.rights.cc | Pas de Licence CC | en_US |
| bordeaux.COinS | ctx_ver=Z39.88-2004&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.jtitle=Pharmaceutics&rft.date=2021-07-28&rft.volume=13&rft.issue=8&rft.eissn=1999-4923&rft.issn=1999-4923&rft.au=CHASTEL,%20Adrien&VIMONT,%20Delphine&CLAVEROL,%20Stephane&ZERNA,%20Marion&BODIN,%20Sacha&rft.genre=article |
