Oncotarget

Research Papers:

Comparison of Immuno-PET of CD138 and PET imaging with 64CuCl2 and 18F-FDG in a preclinical syngeneic model of multiple myeloma

Clément Bailly _, Sébastien Gouard, Marie Lacombe, Patricia Remaud-Le Saëc, Benjamin Chalopin, Mickaël Bourgeois, Nicolas Chouin, Raphaël Tripier, Zakaria Halime, Ferid Haddad, Alain Faivre-Chauvet, Françoise Kraeber-Bodéré, Michel Chérel and Caroline Bodet-Milin

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Oncotarget. 2018; 9:9061-9072. https://doi.org/10.18632/oncotarget.23886

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Abstract

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

Correspondence to:

Michel Chérel, email: [email protected]

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 (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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