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

IF 6.8 1区医学 Q1 CHEMISTRY, MEDICINAL

Journal of Medicinal Chemistry Pub Date : 2025-02-13 DOI:10.1021/acs.jmedchem.4c02672

Mengjing Ji, Xiangwei Wang, Cheng Liu, Guang Ma, Xin Lu, Bin Zhu, Simin He, Jianping Zhang, Xiaoping Xu, Shaoli Song, Zhongyi Yang

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引用次数: 0

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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来源期刊

Journal of Medicinal Chemistry 医学-医药化学

CiteScore

4.00

自引率

11.00%

发文量

804

审稿时长

1.9 months

期刊介绍： The Journal of Medicinal Chemistry is a prestigious biweekly peer-reviewed publication that focuses on the multifaceted field of medicinal chemistry. Since its inception in 1959 as the Journal of Medicinal and Pharmaceutical Chemistry, it has evolved to become a cornerstone in the dissemination of research findings related to the design, synthesis, and development of therapeutic agents. The Journal of Medicinal Chemistry is recognized for its significant impact in the scientific community, as evidenced by its 2022 impact factor of 7.3. This metric reflects the journal's influence and the importance of its content in shaping the future of drug discovery and development. The journal serves as a vital resource for chemists, pharmacologists, and other researchers interested in the molecular mechanisms of drug action and the optimization of therapeutic compounds.