细胞周期依赖性激酶（CDKs），尤其是细胞周期依赖性激酶4/6（CDK4/6），已成为特异性肿瘤显像剂开发的目标。Palbociclib是一种高度选择性的CDK4/6抑制剂。在本研究中，为了开发一种新型的18F标记的Palbociclib衍生物以用于特异性肿瘤显像，我们设计合成了一种配体（NOTA-PBB），该配体由Palbociclib构成作为靶向的药效团，NOTA作为大环双官能团络合剂。通过简单的一步18F标记策略，使用NOTA-AlF螯合化学制备了相应的[18F]AlF-NOTA-PBB复合物，其放射化学纯度（98.4±0.15%）和产率（58.7±4.5%）在35分钟内高达，无需HPLC纯化。放射示踪剂具有脂溶性（log P = 0.095 ± 0.003），在体外和体内具有良好的稳定性。在ER阳性和HER2阴性的MCF-7乳腺癌细胞系上进行的细胞摄取研究表明，放射性摄取被Palbociclib的摩尔剂量预先孵育所阻断，并对CDK4/6具有纳摩尔级的结合亲和力（IC50 = 16.23 ± 1.84 nM），证明了CDK4/6介导的摄取机制。在携带MCF-7肿瘤的裸鼠体内观察到的外显体分布结果显示，[18F]AlF-NOTA-PBB具有明显的肿瘤摄取和高肿瘤/肌肉比率，而且肿瘤摄取与100 μg的Palbociclib抑制相关，证明了对CDK4/6的特异性结合。 PET显像中观察到了[18F]AlF-NOTA-PBB在MCF-7肿瘤中的放射性积累。根据此工作的结果，[18F]AlF-NOTA-PBB具有作为CDK4/6靶向肿瘤显像剂的潜在能力。

Cyclin-dependent kinases (CDKs), especially cyclin-dependent kinase 4/6 (CDK4/6), have been targets for the development of specific tumor imaging agents. Palbociclib is a highly selective CDK4/6 inhibitor. In this study, to develop a novel 18F-labeled palbociclib derivative for specific tumor imaging, we designed and synthesized a ligand (NOTA-PBB) consisting of palbociclib as the targeted pharmacophore and NOTA as the macrocyclic bifunctional chelator. The corresponding [18F]AlF-NOTA-PBB complex was prepared with high radiochemical purity (98.4 ± 0.15%) and yield (58.7 ± 4.5%) within 35 min without requiring HPLC purification through a simple one-step 18F-labeling strategy of NOTA-AlF chelation chemistry. The radiotracer was lipophilic (log P = 0.095 ± 0.003) and had good stability in vitro and in vivo. The cellular uptake studies performed on the MCF-7 breast cancer cell line (ER-positive and HER2-negative) showed that radioactive uptake was blocked by preincubating with a molar dose of palbociclib and it had a nanomolar binding affinity to CDK4/6 (IC50 = 16.23 ± 1.84 nM), demonstrating a CDK4/6-mediated uptake mechanism. Its ex vivo biodistribution in nude mice-bearing MCF-7 tumors showed obvious tumor uptake and a high tumor/muscle ratio of [18F]AlF-NOTA-PBB, and tumor uptake was inhibited with 100 μg of palbociclib, demonstrating specific binding to CDK4/6. Radioactivity accumulation in MCF-7 tumors was observed in PET imaging with [18F]AlF-NOTA-PBB. Based on the results of this work, [18F]AlF-NOTA-PBB has the promising capability as a CDK4/6-targeted tumor imaging agent.