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

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

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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(68Ga)radiolabeled aptamers.The specificity and binding affinity of a radiolabeled aptamer,named 68Ga[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.This study revealed that radiolabeled aptamers are harmless to normal organs and most of them are accumulated in the kidney and cleared from the bladder via urine,which agrees with preclinical studies.Meanwhile,a physiologically based pharmacokinetic model of aptamer was developed,which could potentially predict therapeutic responses and plan personalized treatment strategies.This research studied the biosafety and dynamic pharmacokinetics of aptamers in the human body for the first time,as well as demonstrated the capability of novel molecular imaging fashion in drug development.

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

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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

Department of Nuclear Medicine,Renji Hospital,School of Medicine,Shanghai Jiao Tong University,Shanghai 200127,China

Center for Molecular Imaging Probes,Cancer Research Institute,University of South China,Hengyang,Hunan 421001,China

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

Molecular Science and Biomedicine Laboratory(MBL),State Key Laborat

Shanghai Key Laboratory of Molecular Imaging,Shanghai University of Medicine and Health Sciences,Shanghai 201318,China

Department of Pharmacology and Chemical Biology,Shanghai Jiao Tong University School of Medicine,Shanghai,200127,China

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国家重点研发计划国家重点研发计划国家自然科学基金国家自然科学基金国家自然科学基金国家自然科学基金Shanghai Sailing Program,Shanghai Committee of Science and Technology,ChinaExcellent Academic Leader Programme of Shanghai Health CommissionCore Facility of Basic Medical Sciences in Shanghai Jiao Tong University School of MedicineInnovative Research Team of High-Level Local Universities in Shanghai,China

2020YFA09090002020YFA0210800222041025216116030791953000218278121YF14257002022XD033

2024

10.34133/research.0126

研究(英文)

研究(英文)

CSTPCD
ISSN：
年,卷(期)：2024.2024(1)
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