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

Clément Bailly (1, 2) , Sébastien Gouard (2) , Marie Lacombe (3, 1) , Patricia Remaud-Le Saëc (2) , Benjamin Chalopin (2) , Mickael Bourgeois (4, 1, 2) , Nicolas Chouin (4, 2) , Raphaël Tripier (5) , Zakaria Halime (5) , Ferid Haddad (6, 7) , Alain Faivre-Chauvet (1, 2) , Françoise Kraeber-Bodéré (1, 3, 2) , Michel Chérel (8, 3, 2) , Caroline Bodet-Milin (1, 2)

1 NANTES - Médecine Nucléaire - Département de Médecine Nucléaire
2 CRCINA-ÉQUIPE 13 - Nuclear Oncology
3 UNICANCER/ICO - Institut de Cancérologie de l'Ouest [Angers/Nantes]
4 AMaROC - Animaux modèles pour la recherche en oncologie comparée
5 CEMCA - Chimie, Electrochimie Moléculaires et Chimie Analytique
6 GIP ARRONAX - Accélérateur pour la Recherche en Radiochimie et Oncologie [Nantes Atlantique]
7 SUBATECH - Laboratoire de physique subatomique et des technologies associées
8 Institut de Recherche Public - ARRONAX - (GIP) Groupement d'Intérêt Public [Saint-Herblain]

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.

Mots clés: murine CD138; immuno-PET; multiple myeloma; TE2A-C-functiollaized; syngeneic model; Copper-64

Domaines: Cancer

Clément Bailly, Sébastien Gouard, Marie Lacombe, Patricia Remaud-Le Saëc, Benjamin Chalopin, et al.. Comparison of Immuno-PET of CD138 and PET imaging with 64CuCl2 and 18F-FDG in a preclinical syngeneic model of multiple myeloma. Oncotarget, 2018, 9, pp.9061-9072. ⟨10.18632/oncotarget.23886⟩. ⟨hal-01677118⟩