Development of a CLDN18.2-targeting immuno-PET probe for non-invasive imaging in gastrointestinal tumors
作者机构：Guizhou University Medicine CollegeGuiyang550025China The Ministry of Education Key Laboratory of Carcinogenesis and Translational ResearchNMPA Key Laboratory for Research and Evaluation of RadiopharmaceuticalsDepartment of Nuclear MedicinePeking University Cancer Hospital&InstituteBeijing100142China Department of Biochemistry and Molecular BiologySchool of Basic Medical SciencesSouthwest Medical UniversityLuzhouSichuan646000China Suzhou Transcenta Therapeutics Co.LtdSuzhouJiangsu215127China Institute of Biomedical EngineeringPeking University Shenzhen Graduate SchoolShenzhenGuangdong518055China
出 版 物：《Journal of Pharmaceutical Analysis》 (药物分析学报（英文版）)
年 卷 期：2023年第13卷第4期
页 面：367-375页
核心收录：
学科分类：1007[医学-药学(可授医学、理学学位)] 100701[医学-药物化学] 10[医学]
基 金：The research was funded by the National Natural Science Foundation of China(Grant Nos.:82171973,82171980,and 82102092) Beijing Millions of Talent Projects A Level Funding(Grant No.:2019A38) The study was also supported by Beijing Hospitals Authority Dengfeng Project(Grant No.:DFL20191102) the Pilot Project(4th Round)to Reform Public Development of Beijing Municipal Medical Research Institute(20211) the Third Foster Plan in 2019“Molecular Imaging Probe Preparation and Characterization of Key Technologies and Equipment”for the Development of Key Technologies and Equipment in Major Science and Technology Infrastructure in Shenzhen,China
主 题：Claudin18.2 Gastrointestinal cancers Zirconium-89 Positron emission tomography Good Manufacturing Practices
摘 要：Claudin18.2(CLDN18.2)is a tight junction protein that is overexpressed in a variety of solid tumors such as gastrointestinal cancer and oesophageal *** has been identified as a promising target and a potential biomarker to diagnose tumor,evaluate efficacy,and determine patient ***001 is a recombinant humanized CLDN18.2 antibody that selectively binds to the extracellular loop of human *** this study,we constructed a solid target radionuclide zirconium-^(89)(^(89)Zr)labled-TST001 to detect the expression of in the human stomach cancer BGC823CLDN18.2 cell ***[^(89)Zr]Zr-desferrioxamine(DFO)-TST001 showed high radiochemical purity(RCP,99%)and specific activity(24.15±1.34 GBq/mmol),and was stable in 5%human serum albumin,and phosphate buffer saline(85%RCP at 96 h).The EC_(50) values of TST001 and DFO-TST001 were as high as 0.413±0.055 and 0.361±0.058 nM(P0.05),*** radiotracer had a significantly higher average standard uptake values in CLDN18.2-positive tumors than in CLDN18.2-negative tumors(1.11±0.02 vs.0.49±0.03,P=0.0016)2 days post injection(p.i.).BGC823CLDN18.2 mice models showed high tumor/muscle ratios 96 h ***[^(89)Zr]Zr-DFO-TST001 was much higher than those of the other imaging *** results showed that BGC823CLDN18.2 tumors were highly positive(+++)for CLDN18.2,while those in the BGC823 group did not express CLDN18.2().The results of ex vivo biodistribution studies showed that there was a higher distribution in the BGC823CLDN18.2 tumor bearing mice(2.05±0.16%ID/g)than BGC823 mice(0.69±0.02%ID/g)and blocking group(0.72±0.02%ID/g).A dosimetry estimation study showed that the effective dose of[^(89)Zr]Zr-DFO-TST001 was 0.0705 mSv/MBq,which is within the range of acceptable doses for nuclear medicine *** together,these results suggest that Good Manufacturing Practices produced by this immuno-positron emission tomography probe can detect CLDN18.2-overexpressing tumors.
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