Imaging CDK4/6 Broaden Options of Breast Cancer Diagnostics with Positron Emission Tomography

This study developed a novel PET radiotracer to screen
breast cancer
patients sensitive to CDK4/6 inhibitors, guiding personalized treatment.
Two CDK4/6-targeting precursors were synthesized and evaluated in vitro and in vivo. Three breast cancer
cell linesMCF-7, MDA-MB-231, and MDA-MB-468were selected
based on decreasing sensitivity to palbociclib. Compared to [68Ga]Ga-DOTA-Hexa-CDKi, [68Ga]Ga-DOTA-Bua-CDKi clearly
identified cell lines with high sensitivity to palbociclib. PET/CT
imaging showed significantly higher uptake of [68Ga]Ga-DOTA-Bua-CDKi
(8.40 ± 0.85%ID/g) in MCF-7 tumors 60 min after tracer injection,
with significant differences in tumor uptake among the three models
(P < 0.05). Blocking assays demonstrated specific
tumor uptake of [68Ga]Ga-DOTA-Bua-CDKi. Biosafety tests
validated its safety as a diagnostic agent. [68Ga]Ga-DOTA-Bua-CDKi
showed highly specific targeting of CDK4/6 and effective contrast
imaging in tumor models. To our knowledge, [68Ga]Ga-DOTA-Bua-CDKi
is one of the first radiotracers to assess CDK inhibitor sensitivity,
offering promise for evaluating patient responses to CDK4/6 inhibitors.