“多肽-受体”介导的放射性核素治疗（Peptide Receptor Radionuclide Therapy，PRRT）是近年来国际国内研究的前沿热点。特别是随着177Lu-DOTATATE治疗和177Lu-PSMA-617治疗临床研究的成功及治疗效果被广泛认可，各种优化设计和改进疗效的177Lu治疗新药不断涌现。申请人研究团队前期对用伊文思兰（EB）改构获得的新型177Lu治疗药物177Lu-EB-TATE和177Lu-EB-PSMA开展了初步的剂量学和药效学研究。针对所发现的药效学难题，本项目拟通过对神经内分泌肿瘤和前列腺癌的裸鼠肿瘤模型研究，以及对因难治性神经内分泌肿瘤或前列腺癌行177Lu治疗志愿者的动态显像与疗效评估数据进行深入系统分析，探索“多肽-受体”介导177Lu治疗的药效学机制，建立相应的药代动力学/药效学模型，为进一步推进177Lu治疗新药研发和临床转化打下基础。

Peptide Receptor Radionuclide Therapy (PRRT) is a research focus worldwide in recent years. With the success of clinical trial on 177Lu-DOTATATE therapy in neuroendocrine tumors and 177Lu-PSMA-617 therapy in castration-resistant prostate cancer, many new drugs are emerging to maximize the efficacy and minimize the toxicity. In the preliminary dosimetry study of novel theranostic agents that conjugated a truncated Evans Blue (EB) molecule onto TATE or PSMA, we found there were challenges on the pharmacodynamics of 177Lu therapy, which might be an interesting topic for further investigation. The aim of this study is to investigate the pharmacodynamic mechanism of peptide-receptor mediated 177Lu therapy through evaluating the mouse xenografts models of neuroendocrine tumors and prostate cancer, and as well, analyzing the dynamic imaging data and treatment response to 177Lu-DOTA-EB-TATE and 177Lu-EB-PSMA-617 in patient volunteers with refractory neuroendocrine tumors and castration-resistant prostate cancer, respectively. The study will explore the pharmacological mechanism of 177Lu therapy by comparing these EB-modified radiopharmaceuticals with the original theranostic agents and establishing the corresponding pharmacokinetic/pharmacodynamic models. And then, lay the foundation for further development and clinical transformation of new drug for 177Lu therapy in the future.