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

  • J Med Chem. 2026 Mar 26;69(6):7068-7081. doi: 10.1021/acs.jmedchem.5c03340.
Chunyu Duan  1 ,  Shibo Guo  1 ,  Peng Xu  1 ,  Wei Han  1 ,  Yu Lu  1 ,  Zhide Guo  2 ,  Peng Fu  1 ,  Gang Liu  2 ,  Changjiu Zhao  1
Affiliations
  • 1. Department of Nuclear Medicine, The First Affiliated Hospital of Harbin Medical University, Harbin 150000, China.
  • 2. State Key Laboratory of Vaccines for Infectious Diseases, Center for Molecular Imaging and Translational Medicine, Xiang An Biomedicine Laboratory, School of Public Health, Xiamen University, Xiamen 361102, China.
PMID: 41837524 DOI: 10.1021/acs.jmedchem.5c03340
Abstract

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.

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