Discovery and evaluation of a novel ^(18)F-labeled vasopressin 1a receptor PET ligand with peripheral binding specificity  

作　　者：Junqi Hu Yinlong Li Chenchen Dong Huiyi Wei Kai Liao Junjie Wei Chunyu Zhao Ahmad Chaudhary Jiahui Chen Hao Xu Ke Zhong Steven H.Liang Lu Wang Weijian Ye 

机构地区：[1]Center of Cyclotron and PET Radiopharmaceuticals,Department of Nuclear Medicine&Key Laboratory of Basic and Translational Research on Radiopharmaceuticals,the First Affiliated Hospital of Jinan University,Guangzhou 510630,China [2]Department of Radiology and Imaging Sciences,Emory University,Atlant1,GA 30322,USA [3]Department of Pharmacy,Sun Yat-sen Memorial Hospital,Sun Yat-sen University,Guangzhou 510120,China

出　　处：《Acta Pharmaceutica Sinica B》2024年第9期4014-4027,共14页药学学报（英文版）

基　　金：the National Natural Science Foundation of China(Nos.82071974,82102107,and 82371998);the Science and Technology Program of Guangzhou,China(Nos.202206010106 and 2023A04J1921);the Guangdong Science and Technology Planning Project,China(2022A0505050042).

摘　　要：The arginine-vasopressin(AVP)hormone plays a pivotal role in regulating various physiological processes,such as hormone secretion,cardiovascular modulation,and social behavior.Recent studies have highlighted the V1a receptor as a promising therapeutic target.In-depth insights into V1a receptor-related pathologies,attained through in vivo imaging and quantification in both peripheral organs and the central nervous system(CNS),could significantly advance the development of effective V1a inhibitors.To address this need,we develop a novel V1a-targeted positron emission tomography(PET)ligand,[^(18)F]V1A-2303([^(18)F]8),which demonstrates favorable in vitro binding affinity and selectivity for the V1a receptor.Specific tracer binding in peripheral tissues was also confirmed through rigorous cell uptake studies,autoradiography,biodistribution assessments.Furthermore,[^(18)F]8 was employed in PET imaging and arterial blood sampling studies in healthy rhesus monkeys to assess its brain permeability and specificity,whole-body distribution,and kinetic properties.Our research indicated[^(18)F]8 as a valuable tool for noninvasively studying V1a receptors in peripheral organs,and as a foundational element for the development of next-generation,brain-penetrant ligands specifically designed for the CNS.

关 键 词：VASOPRESSIN AUTISM V1a receptor Positron emission tomography PET imaging RADIOLABELING Fluorine 18 Kinetic modeling 

分 类 号：R749.94[医药卫生—神经病学与精神病学]