A proof-of-concept study on bioorthogonal-based pretargeting and signal amplify radiotheranostic strategy

作者：Hongzhang Yang, Xinying Zeng, Jia Liu, Jingchao Li, Yun Li, Qinglin Zhang, Linlin Shu, Huanhuan Liu, Xueqi Wang, Yuanyuan Liang, Ji Hu, Lumei Huang, Zhide Guo, Xianzhong Zhang · 发表于：Journal of Nanobiotechnology · 年份：2024 · DOI：10.1186/s12951-024-02312-y · 被引用次数：11 · 研究领域：Radiopharmaceutical Chemistry and Applications、Nanoplatforms for cancer theranostics、Prostate Cancer Treatment and Research

Abstract Background Radiotheranostics differs from the vast majority of other cancer therapies in its capacity for simultaneous imaging and therapy, and it is becoming more widely implemented. A balance between diagnostic and treatment requirements is essential for achieving effective radiotheranostics. Herein, we propose a proof-of-concept strategy aiming to address the profound differences in the specific requirements of the diagnosis and treatment of radiotheranostics. Results To validate the concept, we designed an s -tetrazine (Tz) conjugated prostate-specific membrane antigen (PSMA) ligand (DOTA-PSMA-Tz) for 68 Ga or 177 Lu radiolabeling and tumor radiotheranostics, a trans -cyclooctene (TCO) modified Pd@Au nanoplates (Pd@Au-PEG-TCO) for signal amplification, respectively. We then demonstrated this radiotheranostic strategy in the tumor-bearing mice with the following three-step procedures: (1) i.v. injection of the [ 68 Ga]Ga-PSMA-Tz for diagnosis; (2) i.v. injection of the signal amplification module Pd@Au-PEG-TCO; (3) i.v. injection of the [ 177 Lu]Lu-PSMA-Tz for therapy. Firstly, this strategy was demonstrated in 22Rv1 tumor-bearing mice via positron emission tomography (PET) imaging with [ 68 Ga]Ga-PSMA-Tz. We observed significantly higher tumor uptake (11.5 ± 0.8%ID/g) with the injection of Pd@Au-PEG-TCO than with the injection [ 68 Ga]Ga-PSMA-Tz alone (5.5 ± 0.9%ID/g). Furthermore, we validated this strategy through biodistribution studies of [ 177 Lu]Lu-PSMA-Tz,...