Screening for a^(177)Lu-labeled CA19–9 monoclonal antibody via PET imaging for colorectal cancer therapy  

作　　者：Jing Wang Liangang Zhuo Peng Zhao Wei Liao Hongyuan Wei Yuchuan Yang Shuming Peng Xia Yang 

机构地区：[1]Institute of Nuclear Physics and Chemistry,China Academy of Engineering Physics,Mianyang 621900,China [2]NHC Key Laboratory of Nuclear Technology Mediccal Trasnformation(Mianyang Central Hospital),Mianyang 621900,China [3]Key Laboratory of Nuclear Medicine and Molecular Imaging of Sichuan Province,Mianyang 621999,China [4]Department of Nuclear Medicine,The Affiliated Hospital Southwest of Medical University,Luzhou 646000,China

出　　处：《Chinese Chemical Letters》2022年第7期3502-3506,共5页中国化学快报（英文版）

基　　金：supported by the National Natural Science Foundation of China(Nos.21976167,U20A20384);the CAEP Innovation and Development Foundation(No.CX20200003);Nuclear Energy Development Project of State Administration of Science,Technology and Industry for National Defense(No.20201192–1);Key R&D Project of Sichuan Science and Technology Program(No.2020YFS0030);the Central Guidance for Local Science and Technology Development Projects(No.202138–03)。

摘　　要：Carbohydrate antigen 19–9(CA19–9)with multi epitopes relatively high expresses on colorectal cancer(CRC)cells,making it an attractive target for developing radioimmunotherapy(RIT)for CRC.The lutetium-177(^(177)Lu)labeled monoclonal antibodies(mA bs)can selectively bind the corresponding antigens and release targeted cytotoxic radiation,which could induce cell apoptosis and reduce the drug-induced resistance.Here,a series of CA19–9 m Abs were labeled with zirconium-89(^(89)Zr),and one with high tumor uptake was screened via PET imaging,which has potential application for the diagnosis of CRC.Then the screened m Ab(C003)labeled with^(177)Lu was utilized for CA19–9 targeted RIT,which presents a significant suppression effect on the growth of colo205 xenografts than immunotherapy alone.Meanwhile,the side effects of ^(177)Lu-DOTA-C003 are limited according to the results of in vivo study.Both89Zr-DFO-C003for CRC immune-PET imaging and ^(177)Lu-DOTA-C003 for RIT against CRC exhibit good potential in clinical applications.

关 键 词：Lutetium-177 CA19–9 Monoclonal antibody Colorectal cancer RADIOIMMUNOTHERAPY 

分 类 号：R735.34[医药卫生—肿瘤]