What is the Best Radionuclide for Immuno-PET of Multiple Myeloma? A Comparison Study Between 89Zr- and 64Cu-Labeled Anti-CD138 in a Preclinical Syngeneic Model

Clément Bailly (1, 2) , Sébastien Gouard (2) , François Guérard (2) , Benjamin Chalopin (2) , Thomas Carlier (1, 2) , Alain Faivre-Chauvet (2) , Patricia Remaud-Le Saec (2) , Mickaël Bourgeois (1, 3, 2) , Nicolas Chouin (4, 2) , Latifa Rbah-Vidal (2) , Raphaël Tripier (5) , Ferid Haddad (3) , Françoise Kraeber-Bodéré (1, 2) , Caroline Bodet-Milin (1, 2) , Michel Chérel (3, 6, 2)

1 Service de Médecine Nucléaire [Nantes]
2 CRCINA-ÉQUIPE 13 - Nuclear Oncology
3 Institut de Recherche Public - ARRONAX - (GIP) Groupement d'Intérêt Public [Saint-Herblain]
4 ONIRIS - École nationale vétérinaire, agroalimentaire et de l'alimentation Nantes-Atlantique
5 CEMCA - Chimie, Electrochimie Moléculaires et Chimie Analytique
6 Nuclear Medicine Department

Although positron emission tomography (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 for the identification of myeloma cells and could be used in phenotype tumor imaging. In this study, we used an anti-CD138 murine antibody (9E7.4) radiolabeled with copper-64 (64Cu) or zirconium-89 (89Zr) and compared them in a syngeneic mouse model to select the optimal tracers for MM PET imaging. Then, 9E7.4 was conjugated to TE2A-benzyl isothiocyanate (TE2A) and desferrioxamine (DFO) chelators for 64Cu and 89Zr labeling, respectively. 64Cu-TE2A-9E7.4 and 89Zr-DFO-9E7.4 antibodies were evaluated by PET imaging and biodistribution studies in C57BL/KaLwRij mice bearing either 5T33-MM subcutaneous tumors or bone lesions and were compared to 18F-FDG-PET imaging. In biodistribution and PET studies, 64Cu-TE2A-9E7.4 and 89Zr-DFO-9E7.4 displayed comparable good tumor uptake of subcutaneous tumors. On the bone lesions, PET imaging with 64Cu-TE2A-9E7.4 and 89Zr-DFO-9E7.4 showed higher uptake than with 18F-FDG-PET. Comparison of both 9E7.4 conjugates revealed higher nonspecific bone uptakes of 89Zr-DFO-9E7.4 than 64Cu-TE2A-9E7.4. Because of free 89Zr’s tropism for bone when using 89Zr-anti-CD138, 64Cu-anti-CD138 antibody had the most optimal tumor-to-nontarget tissue ratios for translation into humans as a specific new imaging radiopharmaceutical agent in MM.

Nous avons utilisé un anticorps anti-CD138 murin (9E7.4) radiomarqué au cuivre-64 (64Cu) or zirconium-89 (89Zr) et les avons comparés dans un modèle murin syngénique pour sélectionner les traceurs optimaux pour l'imagerie par TEP MM. Ensuite, le 9E7.4 a été conjugué aux agents chélateurs TE2A-isotiocyanate de benzyle (TE2A) et desferrioxamine (DFO) pour les marquages ​​64Cu et 89Zr, respectivement.

Mots clés: multiple myeloma; immuno-PET; copper-64; zirconium-89; murine CD138

Domaines: Radiochimie; Chimie organique; Chimie de coordination

Clément Bailly, Sébastien Gouard, François Guérard, Benjamin Chalopin, Thomas Carlier, et al.. What is the Best Radionuclide for Immuno-PET of Multiple Myeloma? A Comparison Study Between 89Zr- and 64Cu-Labeled Anti-CD138 in a Preclinical Syngeneic Model. International Journal of Molecular Sciences, 2019, 20 (10), pp.2564. ⟨10.3390/ijms20102564⟩. ⟨hal-02141555⟩