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

  • J Med Chem. 2025 Feb 27;68(4):4635-4649. doi: 10.1021/acs.jmedchem.4c02672.
Mengjing Ji  1  2  3  4 ,  Xiangwei Wang  1  2  3  4 ,  Cheng Liu  1  2  3  4 ,  Guang Ma  1  2  3  4 ,  Xin Lu  1  2  3  4 ,  Bin Zhu  1  2  3  4 ,  Simin He  1  2  3  4 ,  Jianping Zhang  1  2  3  4 ,  Xiaoping Xu  1  2  3  4 ,  Shaoli Song  1  2  3  4 ,  Zhongyi Yang  1  2  3  4
Affiliations
  • 1. Department of Nuclear Medicine, Fudan University Shanghai Cancer Center, Shanghai 200032, China.
  • 2. Department of Oncology, Shanghai Medical College, Fudan University, Shanghai 200032, China.
  • 3. Center for Biomedical Imaging, Fudan University, Shanghai 200032, China.
  • 4. Shanghai Engineering Research Center of Molecular Imaging Probes, Shanghai 200032, China.
PMID: 39945599 DOI: 10.1021/acs.jmedchem.4c02672
Abstract

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.

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