The First-in-Human Whole-Body Dynamic Pharmacokinetics Study of Aptamer  

作　　者：Ding Ding Haitao Zhao Dali Wei Qinglai Yang Cai Yang Ruowen Wang Yumei Chen Lianghua Li Shuxian An Qian Xia Gang Huang Jianjun Liu Zeyu Xiao Weihong Tan 

机构地区：[1]Institute of Molecular Medicine(IMM),Renji Hospital,State Key Laboratory of Oncogenes and Related Genes,Shanghai Jiao Tong University School of Medicine,and College of Chemistry and Chemical Engineering,Shanghai Jiao Tong University,Shanghai 200240,China [2]Department of Nuclear Medicine,Renji Hospital,School of Medicine,Shanghai Jiao Tong University,Shanghai 200127,China [3]Center for Molecular Imaging Probes,Cancer Research Institute,University of South China,Hengyang,Hunan 421001,China [4]The Key Laboratory of Zhejiang Province for Aptamers and Theranostics,Zhejiang Cancer Hospital,Hangzhou Institute of Medicine(HIM),Chinese Academy of Sciences,Hangzhou,Zhejiang 310022,China [5]Molecular Science and Biomedicine Laboratory(MBL),State Key Laboratory of Chemo/Biosensing and Chemometrics,College of Chemistry and Chemical Engineering,Hunan University,Changsha,Hunan 410082,China [6]Shanghai Key Laboratory of Molecular Imaging,Shanghai University of Medicine and Health Sciences,Shanghai 201318,China [7]Department of Pharmacology and Chemical Biology,Shanghai Jiao Tong University School of Medicine,Shanghai,200127,China

出　　处：《Research》2024年第1期119-130,共12页研究（英文）

基　　金：the National Key Research and Development Program of China(No.2020YFA0909000 and 2020YFA0210800);the National Science Foundation of China(No.22204102,52161160307,91953000,and 2182781);Shanghai Sailing Program,Shanghai Committee of Science and Technology,China(No.21YF1425700);Excellent Academic Leader Programme of Shanghai Health Commission(2022XD033);Core Facility of Basic Medical Sciences in Shanghai Jiao Tong University School of Medicine,and the Innovative Research Team of High-Level Local Universities in Shanghai,China.

摘　　要：Serving as targeting ligands,aptamers have shown promise in precision medicine.However,the lack of knowledge of the biosafety and metabolism patterns in the human body largely impeded aptamers’clinical translation.To bridge this gap,here we report the first-in-human pharmacokinetics study of protein tyrosine kinase 7 targeted SGC8 aptamer via in vivo PET tracking of gallium-68(^(68)Ga)radiolabeled aptamers.The specificity and binding affinity of a radiolabeled aptamer,named ^(68)Ga[Ga]-NOTA-SGC8,were maintained as proven in vitro.Further preclinical biosafety and biodistribution evaluation confirmed that aptamers have no biotoxicity,potential mutation risks,or genotoxicity at high dosage(40 mg/kg).Based on this result,a first-in-human clinical trial was approved and carried out to evaluate the circulation and metabolism profiles,as well as biosafety,of the radiolabeled SGC8 aptamer in the human body.Taking advantage of the cutting-edge total-body PET,the aptamers’distribution pattern in the human body was acquired in a dynamic fashion.

关 键 词：metabolism DOSAGE WHOLE 

分 类 号：R32[医药卫生—人体解剖和组织胚胎学]