CD38-Targeted Small-Molecule PET Radiotracer for Noninvasive Tumor Evaluation and Preliminary Therapy Monitoring in...

CD38 is an established biomarker for the diagnosis and treatment of various malignancies, including multiple myeloma. Accurate assessment of CD38 expression holds significant clinical value for optimizing CD38-targeted therapies. This study developed a series of small-molecule radiotracers for in vivo assessment of CD38 expression and monitoring of therapeutic response. All ⁶⁸Ga-labeled radiotracers exhibited high radiochemical purity and stability both in vitro and in vivo. PET/CT imaging showed that ⁶⁸Ga-NOTA-MK0159 uptake in multiple myeloma models correlated positively with CD38 expression and could be blocked by excess MK-0159. Notably, daratumumab did not block the uptake of ⁶⁸Ga-NOTA-MK0159 under the experimental conditions of this study, suggesting the probe's potential for assessing CD38 expression during daratumumab therapy. Preclinical studies demonstrated that ⁶⁸Ga-NOTA-MK0159 enables noninvasive whole-body assessment of CD38 in multiple myeloma, which may guide personalized treatment and monitor CD38 expression during daratumumab therapy.