Gao Jie, Wang Yuhao, Wang Ruoqi, Liu Mengya, Wang Hongliang, Li Jianguo, Du Jin
China Institute of Atomic Energy, Beijing, China.
China Institute for Radiation Protection/National Atomic Energy Agency Nuclear Technology (Nonclinical Evaluation of Radiopharmaceuticals) Research and Development Center/CNNC Key Laboratory on Radiotoxicology and Radiopharmaceutical Preclinical Evaluation, Taiyuan, Shanxi, China.
Front Pharmacol. 2025 May 15;16:1576587. doi: 10.3389/fphar.2025.1576587. eCollection 2025.
This study aims to improve the biodistribution of probes and enhance tumor targeting through Ga/Lu-labeled optimized probes, thereby providing better tumor detection and assessment in PET imaging while also exploring their therapeutic effects on tumors.
The physicochemical properties of PARPi probes were optimized through polyethylene glycol (PEG) modification. The tumor inhibition effect of the novel probes was validated through the assessment of affinity, uptake, distribution, and tumor targeting of the PARPi probes. Based on the distribution results, OLINDA/EXM radiation dose estimation was then performed to optimize the clinically administered dose.
In the study, a novel PARP-targeted imaging agent, DOTA-PEG-PARPi, was designed and optimized, demonstrating sufficient stability. The results of trials showed strong affinity and uptake of PEG-PARPi in pancreatic cancer tumor cells. SPECT/CT imaging revealed significant radioactive accumulation, notable uptake, and prolonged retention time in PSN-1 tumors. Tissue distribution results showed that tumor uptake peaked 3 h after administration. According to dose estimation, the highest absorbed dose was observed in the pancreas of female adults.
The PEG-modified PARPi probe not only retained high affinity and targeting capability but also significantly improved retention time during trials.
本研究旨在通过镓/镥标记的优化探针改善探针的生物分布并增强肿瘤靶向性，从而在正电子发射断层显像（PET）成像中实现更好的肿瘤检测和评估，同时探索其对肿瘤的治疗效果。
通过聚乙二醇（PEG）修饰优化聚（ADP-核糖）聚合酶抑制剂（PARPi）探针的理化性质。通过评估PARPi探针的亲和力、摄取、分布和肿瘤靶向性来验证新型探针的肿瘤抑制效果。基于分布结果，然后进行OLINDA/EXM辐射剂量估计以优化临床给药剂量。
在本研究中，设计并优化了一种新型PARP靶向显像剂DOTA-PEG-PARPi，显示出足够的稳定性。试验结果表明PEG-PARPi在胰腺癌细胞中具有很强的亲和力和摄取。单光子发射计算机断层扫描/计算机断层扫描（SPECT/CT）成像显示在PSN-1肿瘤中有明显的放射性积聚、显著摄取和延长的滞留时间。组织分布结果显示给药后3小时肿瘤摄取达到峰值。根据剂量估计，在成年女性胰腺中观察到最高吸收剂量。
PEG修饰的PARPi探针不仅保留了高亲和力和靶向能力，而且在试验期间显著提高了滞留时间。
