Development and Preclinical Evaluation of 68Ga-Labeled BCMA-Targeting Nanobodies for PET Imaging of Multiple Myeloma

B-cell maturation antigen (BCMA) is a critical biomarker for multiple myeloma (MM). In this study, three 68Ga-labeled BCMA-targeting nanobodies (C02, C06, and C07) were developed and evaluated. Protein-based binding assays showed apparent nanomolar affinities, with dissociation constants of 58 ± 7 nM, 87 ± 9 nM, and 33 ± 3 nM, respectively. Their BCMA specificities were confirmed by the high BCMA-positive H929 cell uptakes (6.08 ± 0.73%, 4.59 ± 0.45%, and 4.05 ± 0.29% at 0.5 h, respectively) and significant inhibition (82%, 88%, and 66%, respectively) by the unlabeled nanobodies. [68Ga]Ga-NOTA-BCMA-C07 exhibited the most favorable profile in microPET/CT imaging, with tumor uptake of 3.26 ± 0.19% ID/g, renal uptake of 13.61 ± 1.90% ID/g, and tumor-to-muscle ratio of 7.46 ± 2.82 at 0.5 h post-injection (p.i.). These findings support [68Ga]Ga-NOTA-BCMA-C07 as a promising BCMA-targeted PET radiotracer with potential for further clinical translation.