Annotating CD38 Expression in Multiple Myeloma with [¹⁸F]F–Nb1053

Noninvasive diagnosis of multiple myeloma (MM) is a clinical challenge. CD38 is an established biomarker for MM, and the development of CD38-targeted radiotracers may improve the management of MM. By taking the advantages of bioorthogonal click chemistry, a nanobody (i.e., Nb1053-LLQS) specific for CD38 was successfully labeled with ¹⁸F. The diagnostic efficacy and specificity of the developed tracer (i.e., [¹⁸F]­F–Nb1053) were evaluated by immuno-positron emission tomography (immunoPET) imaging in disseminated MM.1S-bearing models. [¹⁸F]­F–Nb1053 was developed with high radiochemical purity (>98%) and excellent immunoreactivity. [¹⁸F]­F–Nb1053 immunoPET successfully delineated disseminated MM lesions in preclinical MM models. The uptake in the humerus, femur, and tibia was 1.42 ± 0.50%ID/g, 1.35 ± 0.53%ID/g, and 1.48 ± 0.67%ID/g (n = 6), respectively. Tumor uptake of [¹⁸F]­F–Nb1053 decreased after daratumumab premedication, indicating the superior specificity of the reported probe. This work successfully developed a novel CD38-specific probe [¹⁸F]­F–Nb1053 that may potentially optimize the management of MM upon clinical translation.