Comparison of Immuno-PET of CD138 and PET imaging with 64 CuCl 2 and 18 F-FDG in a preclinical syngeneic model of multiple myeloma

// Clement Bailly 1, 2, * , Sebastien Gouard 2, * , Marie Lacombe 1, 3 , Patricia Remaud-Le Saec 2 , Benjamin Chalopin 2 , Mickael Bourgeois 1, 2, 4 , Nicolas Chouin 2, 5 , Raphael Tripier 6 , Zakaria Halime 6 , Ferid Haddad 4 , Alain Faivre-Chauvet 1, 2 , Francoise Kraeber-Bodere 1, 2, 3 , Michel Cherel 2, 3, 4, * and Caroline Bodet-Milin 1, 2, * 1 Nuclear Medicine Department, University Hospital, Nantes, France 2 Nantes-Angers Cancer Research Center CRCINA, University of Nantes, INSERM UMR1232, CNRS-ERL6001, Nantes, France 3 Nuclear Medicine Department, ICO-Rene Gauducheau Cancer Center, Saint-Herblain, France 4 Groupement d’Interet Public ARRONAX, Saint-Herblain, France 5 AMaROC, Oniris, Ecole Nationale Veterinaire, Agroalimentaire et de l'Alimentation de Nantes-Atlantique, Nantes, France 6 CNRS-UMR6521, University of Bretagne Occidentale, Brest, France * These authors contributed equally to this work Correspondence to: Michel Cherel, email: Michel.Cherel@univ-nantes.fr Keywords: multiple myeloma; immuno-PET; copper-64; murine CD138; syngeneic model Received: May 07, 2017      Accepted: November 10, 2017      Published: January 03, 2018 ABSTRACT Purpose: Although recent data from the literature suggest that PET imaging with [18]-Fluorodeoxyglucose ( 18 F-FDG) is a promising technique in multiple myeloma (MM), the development of other radiopharmaceuticals seems relevant. CD138 is currently used as a standard marker in many laboratories for the identification and purification of myeloma cells, and could be used in phenotype tumor imaging. In this study, we evaluated a 64 Cu-labeled anti-CD138 murine antibody ( 64 Cu-TE2A-9E7.4) and a metabolic tracer ( 64 CuCl 2 ) for PET imaging in a MM syngeneic mouse model. Experimental Design and Results: 64 Cu-TE2A-9E7.4 antibody and 64 CuCl2 were evaluated via PET imaging and biodistribution studies in C57BL / KaLwRij mice bearing either 5T33-MM subcutaneous tumors or bone lesions. These results were compared to 18F-FDG-PET imaging. Autoradiography and histology of representative tumors were secondly conducted. In biodistribution and PET studies, 64 Cu-TE2A-9E7.4 displayed good tumor uptake of subcutaneous and intra-medullary lesions, greater than that demonstrated with 18 F-FDG-PET. In control experiments, only low-level, non-specific uptake of 64 Cu-labeled isotype IgG was observed in tumors. Similarly, low activity concentrations of 64 CuCl 2 were accumulated in MM lesions. Histopathologic analysis of the immuno-PET–positive lesions revealed the presence of plasma cell infiltrates within the bone marrow. Conclusions: 64 Cu-labeled anti-CD138 antibody can detect subcutaneous MM tumors and bone marrow lesions with high sensitivity, outperforming 18 F-FDG-PET and 64 CuCl 2 in this preclinical model. These data support 64 Cu-anti-CD138 antibody as a specific and promising new imaging radiopharmaceutical agent in MM.