Comparison of Immuno-PET of CD138 and PET imaging with 64CuCl2 and 18F-FDG in a preclinical syngeneic model of multiple myeloma
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Clément Bailly1,2,*, Sébastien Gouard2,*, Marie Lacombe1,3, Patricia Remaud-Le Saëc2, Benjamin Chalopin2, Mickaël Bourgeois1,2,4, Nicolas Chouin2,5, Raphaël Tripier6, Zakaria Halime6, Ferid Haddad4, Alain Faivre-Chauvet1,2, Françoise Kraeber-Bodéré1,2,3, Michel Chérel2,3,4,* and Caroline Bodet-Milin1,2,*
1Nuclear Medicine Department, University Hospital, Nantes, France
2Nantes-Angers Cancer Research Center CRCINA, University of Nantes, INSERM UMR1232, CNRS-ERL6001, Nantes, France
3Nuclear Medicine Department, ICO-René Gauducheau Cancer Center, Saint-Herblain, France
4Groupement d’Intérêt Public ARRONAX, Saint-Herblain, France
5AMaROC, Oniris, Ecole Nationale Vétérinaire, Agroalimentaire et de l'Alimentation de Nantes-Atlantique, Nantes, France
6CNRS-UMR6521, University of Bretagne Occidentale, Brest, France
*These authors contributed equally to this work
Michel Chérel, 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
Purpose: Although recent data from the literature suggest that PET imaging with -Fluorodeoxyglucose (18F-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 64Cu-labeled anti-CD138 murine antibody (64Cu-TE2A-9E7.4) and a metabolic tracer (64CuCl2) for PET imaging in a MM syngeneic mouse model.
Experimental Design and Results: 64Cu-TE2A-9E7.4 antibody and 64CuCl2 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, 64Cu-TE2A-9E7.4 displayed good tumor uptake of subcutaneous and intra-medullary lesions, greater than that demonstrated with 18F-FDG-PET. In control experiments, only low-level, non-specific uptake of 64Cu-labeled isotype IgG was observed in tumors. Similarly, low activity concentrations of 64CuCl2 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: 64Cu-labeled anti-CD138 antibody can detect subcutaneous MM tumors and bone marrow lesions with high sensitivity, outperforming 18F-FDG-PET and 64CuCl2 in this preclinical model. These data support 64Cu-anti-CD138 antibody as a specific and promising new imaging radiopharmaceutical agent in MM.
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