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

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.