新型γH2AX靶向分子探针的研发及其用于前列腺癌放射核性素治疗疗效预测的探索

PSMA （前列腺特异性膜抗原）放射性配体治疗（PRLT）是转移性去势抵抗性前列腺癌（mCRPC）治疗的一种新方法，然而，PSMA PET用于PRLT疗效预测尚存在不足。本项目拟从DNA损伤与修复的角度探讨部分中、高等程度PSMA表达的肿瘤对PRLT不敏感的机制。针对γH2AX这一DNA双链断裂标志物，开发一种制备更简单的PET分子探针124I-anti-γ-H2AX-Tat，通过细胞、动物实验研究其摄取与γ-H2AX蛋白表达量及PRLT疗效之间的关系；结合申请人已开发的PSMA分子探针Al18F-PSMA-BCH，有望为mCRPC患者的PRLT预后及疗效预测提供新的方法，并为治疗方案的制定提供参考。

PSMA (prostate specific membrane antigen) radioligand therapy (PRLT) is a new method for the treatment of metastatic castration resistant prostate cancer (mCRPC). However, there are still some deficiencies in the application of PSMA PET in predicting the efficacy of PRLT. The purpose of this project is to explore the mechanism of PRLT insensitivity in some tumors with medium or high PSMA expression from the aspect of DNA damage and repair. In this project, we plan to develop a γH2AX, DNA double strand break marker, targeted PET probe, 124I-anti-γ-H2AX-Tat, which can be prepared with simpler preparation method. Study the relationship between its uptake and the expression of γH2AXprotein or the efficacy of PRLT by cellular and animal studies. Combining with the PSMA probe, Al18F-PSMA-BCH, developed by the applicant, we expect to provide a new method for the prognosis and predicting efficacy of PRLT for patients with mCRPC，and provide reference for making treatment plans.