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Article Abstract
Cyclin-dependent kinase 19 (CDK19) has been identified as a promising target due to its high expression in prostate cancer (PCa) cells. This study focuses on optimizing the structure of CDK19-targeted imaging tracers. The linker of the lead compound was optimized based on previous structure-activity relationships and cyclization strategy. Incorporating the spirocyclic structure optimized the binding conformation and increased the binding effect of the ligands, which was also reflected in its increased IC value. Mice imaging showed clearer tumor lesions and acceptable tissue safety. In addition, Ga- identified three distinct lesions in two advanced CRPC patients, located in the pelvis, sacrum, and prostate. The SUVmax values of these lesions were 3.31, 2.93, and 2.73, respectively, with tumor-to-nontumor (T/NT) ratios of 2.30, 2.59, and 2.42. In conclusion, Ga- not only effectively detected lesions in PCa patients, but also preliminarily demonstrated tissue safety, further highlighting the potential of CDK19 in PCa diagnosis.
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| http://dx.doi.org/10.1021/acs.jmedchem.5c01389 | DOI Listing |
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