Safety,pharmacokinetics,and dosimetry of^(177)Lu-AB-3PRGD2 in patients with advanced integrinα_(v)β_(3)-positive tumors:A first-in-human study  

作　　者：Huimin Sui Feng Guo Hongfei Liu Rongxi Wang Linlin Li Jiarou Wang Chenhao Jia Jialin Xiang Yingkui Liang Xiaohong Chen Zhaohui Zhu Fan Wang 

机构地区：[1]Department of Nuclear Medicine,State Key Laboratory of Complex Severe and Rare Diseases,Beijing Key Laboratory of Molecular Targeted Diagnosis and Therapy in Nuclear Medicine,Peking Union Medical College Hospital,Chinese Academy of Medical Sciences,Peking Union Medical College,Beijing 100730,China [2]Department of Nuclear Medicine,Sixth Medical Center of PLA General Hospital,Beijing 100048,China [3]Department of Otolaryngology-Head and Neck Surgery,Beijing Tongren Hospital,Capital Medical University,Beijing 100730,China [4]Medical Isotopes Research Center and Department of Radiation Medicine,State Key Laboratory of Natural and Biomimetic Drugs,School of Basic Medical Sciences,International Cancer Institute,Peking University,Beijing 100191,China

出　　处：《Acta Pharmaceutica Sinica B》2025年第2期669-680,共12页药学学报(英文版)

基　　金：supported by Chinese Academy of Medical Science Innovation Fund for Medical Sciences(2022-I2M-2-002);the National High-Level Hospital Clinical Research Funding(2022-PUMCH-D-002,China);Clinical and translational medicine research project of the Chinese Academy of Medical Sciences(2022-I2M-C&T-A-008,China),the National Natural Science Foundation of China(82272046);the Fundamental Research Funds for the Central Universities(3332023124,China).

摘　　要：Integrinα_(v)β_(3)is overexpressed in various tumor cells and angiogenesis.To date,no drug has been proven to target it for therapy.A first-in-human study was designed to investigate the safety,pharmacokinetics,and dosimetry of^(177)Lu-AB-3PRGD2,a novel integrinα_(v)β_(3)-targeting radionuclide drug with an albumin-binding motif to optimize the pharmacokinetics.Ten patients(3 men,7 women;aged 45±16 years)with integrinα_(v)β_(3)-avid tumors were recruited to accept^(177)Lu-AB-3PRGD2 injection in a dosage of 1.57±0.08 GBq(42.32±2.11 mCi),followed by serial scans to obtain its dynamic distribution in the body.Safety tests were performed before and every 2 weeks after the treatment for 6-8 weeks.No adverse event over grade 3 was observed.^(177)Lu-AB-3PRGD2 was excreted mainly through the urinary system,with intense radioactivity in the kidneys and bladder.Moderate distribution was found in the liver,spleen,and intestines.The estimated blood half-life was 2.85±2.17 h.The whole-body effective dose was 0.251±0.047 mSv/MBq.The absorbed doses were 0.157±0.032 mGy/MBq in red bone marrow and 0.684±0.132 mGy/MBq in kidneys.This first-in-human study of^(177)Lu-AB-3PRGD2 treatment indicates its promising potential for targeted radionuclide therapy of integrinα_(v)β_(3)-avid tumors.It merits further studies in more patients with escalating doses and multiple treatment courses.

关 键 词：^(177)Lu-AB-3PRGD2 Integrinα_(v)β_(3) Targeted radionuclide therapy First-in-human study PHARMACOKINETICS DOSIMETRY Safety Advanced tumors 

分 类 号：R730.5[医药卫生—肿瘤]