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The Use of a Non-Conventional Long-Lived Gallium Radioisotope 66Ga Improves Imaging Contrast of EGFR Expression in Malignant Tumours Using DFO-ZEGFR:2377 Affibody Molecule
Article

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

1
INCIA, University of Bordeaux, CNRS, EPHE, UMR 5287, F-33000 Bordeaux, France
2
Nuclear Medicine Department, University Hospital of Bordeaux, F-33000 Bordeaux, France
3
Proteome Platform, University Bordeaux, F-33000 Bordeaux, France
4
Life Molecular Imaging (Formely Piramal Imaging) GmbH, 13353 Berlin, Germany
*
Author to whom correspondence should be addressed.
Academic Editor: Björn Wängler
Pharmaceutics 2021, 13(8), 1160; https://doi.org/10.3390/pharmaceutics13081160
Received: 12 May 2021 / Revised: 13 July 2021 / Accepted: 22 July 2021 / Published: 28 July 2021
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. View Full-Text
Keywords: GRP-R; 68Ga; PET; kit GRP-R; 68Ga; PET; kit
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MDPI and ACS Style

Chastel, A.; Vimont, D.; Claverol, S.; Zerna, M.; Bodin, S.; Berndt, M.; Chaignepain, S.; Hindié, E.; Morgat, C. 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, 13, 1160. https://doi.org/10.3390/pharmaceutics13081160

AMA Style

Chastel A, Vimont D, Claverol S, Zerna M, Bodin S, Berndt M, Chaignepain S, Hindié E, Morgat C. 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; 13(8):1160. https://doi.org/10.3390/pharmaceutics13081160

Chicago/Turabian Style

Chastel, Adrien, Delphine Vimont, Stephane Claverol, Marion Zerna, Sacha Bodin, Mathias Berndt, Stéphane Chaignepain, Elif Hindié, and Clément Morgat. 2021. "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 13, no. 8: 1160. https://doi.org/10.3390/pharmaceutics13081160

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