Preclinical Evaluation of a <sup>64</sup>Cu-Based Theranostic Approach in a Murine Model of Multiple Myeloma
Although the concept of theranostics is neither new nor exclusive to nuclear medicine, it is a particularly promising approach for the future of nuclear oncology. This approach is based on the use of molecules targeting specific biomarkers in the tumour or its microenvironment, associated with optim...
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| Format: | Article |
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MDPI AG
2023-06-01
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| Series: | Pharmaceutics |
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| Online Access: | https://www.mdpi.com/1999-4923/15/7/1817 |
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| author | Cassandra Métivier Patricia Le Saëc Joëlle Gaschet Catherine Chauvet Séverine Marionneau-Lambot Peter O. Hofgaard Bjarne Bogen Julie Pineau Nathalie Le Bris Raphaël Tripier Cyrille Alliot Férid Haddad Michel Chérel Nicolas Chouin Alain Faivre-Chauvet Latifa Rbah-Vidal |
| author_facet | Cassandra Métivier Patricia Le Saëc Joëlle Gaschet Catherine Chauvet Séverine Marionneau-Lambot Peter O. Hofgaard Bjarne Bogen Julie Pineau Nathalie Le Bris Raphaël Tripier Cyrille Alliot Férid Haddad Michel Chérel Nicolas Chouin Alain Faivre-Chauvet Latifa Rbah-Vidal |
| author_sort | Cassandra Métivier |
| collection | DOAJ |
| description | Although the concept of theranostics is neither new nor exclusive to nuclear medicine, it is a particularly promising approach for the future of nuclear oncology. This approach is based on the use of molecules targeting specific biomarkers in the tumour or its microenvironment, associated with optimal radionuclides which, depending on their emission properties, allow the combination of diagnosis by molecular imaging and targeted radionuclide therapy (TRT). Copper-64 has suitable decay properties (both β<sup>+</sup> and β- decays) for PET imaging and potentially for TRT, making it both an imaging and therapy agent. We developed and evaluated a theranostic approach using a copper-64 radiolabelled anti-CD138 antibody, [<sup>64</sup>Cu]Cu-TE1PA-9E7.4 in a MOPC315.BM mouse model of multiple myeloma. PET imaging using [<sup>64</sup>Cu]Cu-TE1PA-9E7.4 allows for high-resolution PET images. Dosimetric estimation from ex vivo biodistribution data revealed acceptable delivered doses to healthy organs and tissues, and a very encouraging tumour absorbed dose for TRT applications. Therapeutic efficacy resulting in delayed tumour growth and increased survival without inducing major or irreversible toxicity has been observed with 2 doses of 35 MBq administered at a 2-week interval. Repeated injections of [<sup>64</sup>Cu]Cu-TE1PA-9E7.4 are safe and can be effective for TRT application in this syngeneic preclinical model of MM. |
| first_indexed | 2024-03-11T00:45:29Z |
| format | Article |
| id | doaj.art-e9ef0bbdb1f6481592abe4acf5b206e8 |
| institution | Directory Open Access Journal |
| issn | 1999-4923 |
| language | English |
| last_indexed | 2024-03-11T00:45:29Z |
| publishDate | 2023-06-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Pharmaceutics |
| spelling | doaj.art-e9ef0bbdb1f6481592abe4acf5b206e82023-11-18T20:54:16ZengMDPI AGPharmaceutics1999-49232023-06-01157181710.3390/pharmaceutics15071817Preclinical Evaluation of a <sup>64</sup>Cu-Based Theranostic Approach in a Murine Model of Multiple MyelomaCassandra Métivier0Patricia Le Saëc1Joëlle Gaschet2Catherine Chauvet3Séverine Marionneau-Lambot4Peter O. Hofgaard5Bjarne Bogen6Julie Pineau7Nathalie Le Bris8Raphaël Tripier9Cyrille Alliot10Férid Haddad11Michel Chérel12Nicolas Chouin13Alain Faivre-Chauvet14Latifa Rbah-Vidal15Nantes Université, Inserm, CNRS, Université d’Angers, CRCI<sup>2</sup>NA, 44007 Nantes, FranceNantes Université, Inserm, CNRS, Université d’Angers, CRCI<sup>2</sup>NA, 44007 Nantes, FranceNantes Université, Inserm, CNRS, Université d’Angers, CRCI<sup>2</sup>NA, 44007 Nantes, FranceNantes Université, Inserm, CNRS, Université d’Angers, CRCI<sup>2</sup>NA, 44007 Nantes, FranceNantes Université, Inserm, CNRS, Université d’Angers, CRCI<sup>2</sup>NA, CHU Nantes, 44007 Nantes, FranceDepartment of Immunology, Oslo University Hospital, 04024 Oslo, NorwayDepartment of Immunology, Oslo University Hospital, 04024 Oslo, NorwayUniv. Brest, UMR CNRS 6521 CEMCA, 6 Avenue Victor le Gorgeu, 29200 Brest, FranceUniv. Brest, UMR CNRS 6521 CEMCA, 6 Avenue Victor le Gorgeu, 29200 Brest, FranceUniv. Brest, UMR CNRS 6521 CEMCA, 6 Avenue Victor le Gorgeu, 29200 Brest, FranceNantes Université, Inserm, CNRS, Université d’Angers, CRCI<sup>2</sup>NA, 44007 Nantes, FranceIMT Atlantique, Nantes Université, Subatech, 44307 Nantes, FranceNantes Université, Inserm, CNRS, Université d’Angers, CRCI<sup>2</sup>NA, 44007 Nantes, FranceNantes Université, Inserm, CNRS, Université d’Angers, Oniris, CRCI<sup>2</sup>NA, 44007 Nantes, FranceNantes Université, Inserm, CNRS, Université d’Angers, CRCI<sup>2</sup>NA, CHU Nantes, 44007 Nantes, FranceNantes Université, Inserm, CNRS, Université d’Angers, CRCI<sup>2</sup>NA, 44007 Nantes, FranceAlthough the concept of theranostics is neither new nor exclusive to nuclear medicine, it is a particularly promising approach for the future of nuclear oncology. This approach is based on the use of molecules targeting specific biomarkers in the tumour or its microenvironment, associated with optimal radionuclides which, depending on their emission properties, allow the combination of diagnosis by molecular imaging and targeted radionuclide therapy (TRT). Copper-64 has suitable decay properties (both β<sup>+</sup> and β- decays) for PET imaging and potentially for TRT, making it both an imaging and therapy agent. We developed and evaluated a theranostic approach using a copper-64 radiolabelled anti-CD138 antibody, [<sup>64</sup>Cu]Cu-TE1PA-9E7.4 in a MOPC315.BM mouse model of multiple myeloma. PET imaging using [<sup>64</sup>Cu]Cu-TE1PA-9E7.4 allows for high-resolution PET images. Dosimetric estimation from ex vivo biodistribution data revealed acceptable delivered doses to healthy organs and tissues, and a very encouraging tumour absorbed dose for TRT applications. Therapeutic efficacy resulting in delayed tumour growth and increased survival without inducing major or irreversible toxicity has been observed with 2 doses of 35 MBq administered at a 2-week interval. Repeated injections of [<sup>64</sup>Cu]Cu-TE1PA-9E7.4 are safe and can be effective for TRT application in this syngeneic preclinical model of MM.https://www.mdpi.com/1999-4923/15/7/1817theranosticscopper-64PET imagingtargeted radionuclide therapydosimetryCD138 |
| spellingShingle | Cassandra Métivier Patricia Le Saëc Joëlle Gaschet Catherine Chauvet Séverine Marionneau-Lambot Peter O. Hofgaard Bjarne Bogen Julie Pineau Nathalie Le Bris Raphaël Tripier Cyrille Alliot Férid Haddad Michel Chérel Nicolas Chouin Alain Faivre-Chauvet Latifa Rbah-Vidal Preclinical Evaluation of a <sup>64</sup>Cu-Based Theranostic Approach in a Murine Model of Multiple Myeloma Pharmaceutics theranostics copper-64 PET imaging targeted radionuclide therapy dosimetry CD138 |
| title | Preclinical Evaluation of a <sup>64</sup>Cu-Based Theranostic Approach in a Murine Model of Multiple Myeloma |
| title_full | Preclinical Evaluation of a <sup>64</sup>Cu-Based Theranostic Approach in a Murine Model of Multiple Myeloma |
| title_fullStr | Preclinical Evaluation of a <sup>64</sup>Cu-Based Theranostic Approach in a Murine Model of Multiple Myeloma |
| title_full_unstemmed | Preclinical Evaluation of a <sup>64</sup>Cu-Based Theranostic Approach in a Murine Model of Multiple Myeloma |
| title_short | Preclinical Evaluation of a <sup>64</sup>Cu-Based Theranostic Approach in a Murine Model of Multiple Myeloma |
| title_sort | preclinical evaluation of a sup 64 sup cu based theranostic approach in a murine model of multiple myeloma |
| topic | theranostics copper-64 PET imaging targeted radionuclide therapy dosimetry CD138 |
| url | https://www.mdpi.com/1999-4923/15/7/1817 |
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