Development and Preclinical Validation of a Novel 89Zr-Labeled BCMA-Targeting Antibody for ImmunoPET Imaging: Application in Multiple Myeloma Models and First-In-Nonhuman-Primates.

B-cell maturation antigen (BCMA) is a clinically validated biomarker and therapeutic target in multiple myeloma (MM). Here, we report the design, synthesis, and preclinical evaluation of an immunoPET probe, [89Zr]Zr-DFO-PFBH0L0, derived from a novel humanized anti-BCMA monoclonal antibody. The antibody was conjugated with deferoxamine (DFO) and radiolabeled with zirconium-89 (89Zr), yielding a probe with excellent in vitro stability. The tracer retained high binding affinity and demonstrated specific binding to BCMA-positive MM cell lines. In vivo PET imaging and biodistribution studies demonstrated significantly higher tumor uptake in H929-bearing BCMA xenografts (10.04 ± 1.04% ID/g) and a tumor-to-blood ratio exceeding 88, outperforming all controls. Notably, this study presents the first BCMA-targeted PET/CT imaging in nonhuman primates (rhesus macaques), revealing favorable pharmacokinetics, biodistribution, and metabolic stability - underscoring its translational potential for clinical immunoPET imaging and therapeutic monitoring. These results establish [89Zr]Zr-DFO-PFBH0L0 as a promising immunoPET imaging agent for noninvasive, whole-body evaluation of BCMA-expressing malignancies.