Abstract

B cell maturation antigen (BCMA) is a promising theranostic target for multiple myeloma (MM). BCMA-targeted therapeutics, such as antibody–drug conjugates and chimeric antigen receptor T-cell immunotherapies, are rapidly reshaping the treatment landscape of MM. Along with the progress, a critical challenge is to noninvasively visualize the dynamic change of BCMA for a better-personalized prescription of the above-mentioned therapeutics. We aim to develop immuno-positron emission tomography (immunoPET) imaging strategies to visualize BCMA expression and realize target-specific diagnosis of MM in the work. A series of BCMA-targeting nanobodies were produced and two of them were successfully labeled with gallium-68 (68Ga). MM models were established using MM.1S cell line and NOD-Prkdcem26Cd52Il2rgem26Cd22/Nju mice. The diagnostic efficacies of the developed probes (i.e., [68Ga]Ga-NOTA-MMBC2 and [68Ga]Ga-NOTA-MMBC3) were investigated in disseminated MM models by immunoPET imaging, region of interest analysis on PET images, biodistribution study, and histopathological staining study. [68Ga]Ga-NOTA-MMBC2 and [68Ga]Ga-NOTA-MMBC3 were developed with radiochemical purities of >99%. ImmunoPET imaging with either [68Ga]Ga-NOTA-MMBC2 or [68Ga]Ga-NOTA-MMBC3 precisely visualized BCMA expression and delineated MM lesions throughout the bone marrows. Moreover, [68Ga]Ga-NOTA-MMBC3 immunoPET successfully detected remnant MM after treatment with daratumumab, a prescription medicine used to treat MM. The immunoPET imaging data correlated well with the biodistribution and immunohistochemistry staining results. The work successfully developed two state-of-the-art BCMA-targeted radiotracers for annotating BCMA expression and diagnosing MM. Translational studies interpreting the diagnostic efficacies of the immunoPET radiotracers are warranted.