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

Abstract

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.