Covalent multi-targeted radiopharmaceuticals for enhanced tumor theranostics  

作　　者：Yirui Guo Zhengzhong Lv Yuqi Zhang Zhongsheng Zhao Yurong Fan Yan Chen Miao Li Xingxiang Ren Yiming Feng Zhixin Han Hongyuan Wen Guohua Fan Ru Yang Haibin Shi 

机构地区：[1]State Key Laboratory of Radiation Medicine and Protection,School for Radiological and Interdisciplinary Sciences(RAD-X)and Collaborative Innovation Centre of Radiation Medicine of Jiangsu Higher Education Institutions,Soochow University,Suzhou 215123,China [2]Department of Rheumatology and Immunology,The Second Afiliated Hospital of Soochow University,Suzhou 215004,China [3]Department of Radiology,The Second Afiliated Hospital of Soochow University,Suzhou 215004,China

出　　处：《Science China Chemistry》2025年第4期1456-1467,共12页中国科学(化学英文版)

基　　金：supported by the National Natural Science Foundation of China(T2325019,22077092);the Basic Research Program of Jiangsu(BK20243030);the Special Project of“Technological Innovation”Project of CNNC Medical Industry Co.Ltd.(ZHYLYB2021001);the Four“Batches"Innovation Project of Invigorating Medical through Science and Technology of Shanxi Province(2022XM19);the Open Project Program of the State Key Laboratory of Radiation Medicine and Protection(GZK12024016,GZK12023050,GZK12024013);a Project funded by the Priority Academic Program Development of Jiangsu Higher Education Institutions.

摘　　要：Tumor-targeted radiopharmaceuticals have become an attractive modality for tumor diagnosis and treatment in clinics.However;their wide clinical applications are seriously impeded by poor tumor targeting;rapid systemic clearance;and short tumor retention.Therefore;developing advanced radiopharmaceuticals with great tumor specificity and prolonged retention time is highly desirable for efficient tumor treatment.Herein;we report a tumor-targeted covalently anchoring strategy that selectively crosslinks the radiopharmaceuticals to intratumoral macromolecules for prolonged tumor theranostics.A covalent multi-targeted radiopharmaceutical(CMTR)d-IR-2(^(125)IRGD)that includes a sulfenic acid-reactive 1;3-cyclohexanedione group was developed.We demonstrated this probe could specifically accumulate at the tumor site and bind to the sulfenated proteins that are overexpressed within tumors;which greatly prevents the efflux of probes in tumor tissues while having faster clearance in healthy tissues resulting in 12 h longer tumor retention than conventional probes for sensitive NIR and SPECT/CT detection of tumors in vivo.More notably;the 131I-labeled probe could significantly suppress the growth of lung tumor A549.We thus envision that this work may offer a promising approach to developing effective radiopharmaceuticals for precise diagnosis and treatment of various tumors.

关 键 词：covalent targeted radiopharmaceuticals sulfenated protein nuclear imaging lung cancer THERANOSTICS 

分 类 号：R730.5[医药卫生—肿瘤]