Optimized CDK19 PET Tracers: Spirocyclic-Driven Design and Prostate Cancer Imaging

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 IC50 value. Mice imaging showed clearer
tumor lesions and acceptable tissue safety. In addition, 68Ga-IRM-8c 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, 68Ga-IRM-8c not only effectively detected lesions
in PCa patients, but also preliminarily demonstrated tissue safety,
further highlighting the potential of CDK19 in PCa diagnosis.