靶向性肿瘤分子探针是当今放射性药物的研究热点。就细胞周期蛋白依赖性激酶4/6 (CDK4/6)而言，CDK4/6是细胞周期调节的一类重要激酶，因其在多种肿瘤中活性增强，成为抗肿瘤药物研发的关键靶点。CDK4/6抑制剂能与CDK4/6特异性结合发挥抑制作用，因此围绕CDK4/6抑制剂来构建新型放射性核素标记肿瘤分子探针具有可行性和重要意义。考虑到Palbociclib是目前唯一被批准上市的CDK4/6抑制剂，本项目在保留Palbociclib药效团的基础上，以CDK4/6为靶点，选择临床最常用的99mTc和18F作为标记核素，通过配体结构修饰和标记策略优化以期获得靶向CDK4/6的新型SPECT/PET肿瘤分子探针。该类分子探针将在肿瘤早期诊断、个性化治疗以及CDK4/6抑制剂靶向治疗的疗效监测方面发挥重要作用。项目注重原创性与实用性的结合，具有重要的科学意义和良好的应用前景。

Targeted tumor molecular probes are hot spots in the field of current radiopharmaceuticals. As for cyclin dependent kinases 4/6(CDK4/6), they are a class of important kinases for regulating cell cycle progression. The activities of CDK4/6 are often upregulated in many kinds of tumors, thus making them key targets for the development of anticancer drugs. CDK4/6 inhibitors can selectively inhibit CDK4/6, so the construction of novel radiolabeled CDK4/6 inhibitors as tumor molecular probes is feasible and has important significance. Considering palbociclib is currently the only approved CDK4/6 inhibitor on the market, this project expects to obtain novel SPECT/PET tumor molecular probes for targeting CDK4/6 by taking CDK4/6 as the targets, reserving the pharmacophore of palbociclib, choosing the most commonly used radionuclides( 99mTc and 18F) to be labeling nuclides, and using ligand structure modification and labeling strategy optimization. The proposed molecular probes will play an important role in the early diagnosis of tumor, personalized therapy and the monitoring of therapy efficiency of targeted therapy with CDK4/6 inhibitors. The project thinks highly of the combination of originality and practicality and it has important scientific significance and good prospects for application.