原子能科学技术2026，Vol.60Issue(z1)：18-28,11.DOI:10.7538/yzk.2026.youxian.0210
177Lu标记的靶向CLDN18.2放射免疫药物制备及生物学评价
Preparation and Biological Evaluation of 177Lu-labeled Radioimmunoconjugate Targeting CLDN18.2
摘要
Abstract
CLDN18.2 exhibits specific high expression in various solid tumors,such as gastric and pancreatic cancers,and has emerged as a widely investigated anti-tumor drug target in recent years.In this study,a 177Lu-labeled radioimmunotherapy agent targeting CLDN18.2,177Lu-DOTA-h1D6,was constructed,and its in vitro stability,in vivo biodistribution in tumor-bearing mice,Micro-SPECT/CT imaging performance,and anti-tumor efficacy were preliminarily evaluated.The fully humanized monoclonal antibody h1D6 with high affinity for CLDN18.2 was modified with the bifunctional chelator(p-SCN-Bn-DOTA)and labeled with the radionuclide 177Lu.Gentisic acid was introduced into the reaction system as a radiostabilizer,and the 177Lu-DOTA-h1D6 conjugate was obtained after purification.The results show that the radiochemical purity(RCP)of 177Lu-DOTA-h1D6 is greater than 95％,and the partition coefficient(lg D)is-3.16±0.09,indicating good hydrophilicity.The in vitro stability results indicate that the RCP remains above 95％after 168 h of incubation at 37℃,demonstrating good in vitro stability.The biodistribution results in tumor-bearing mice show that 177Lu-DOTA-h1D6 is rapidly and specifically taken up in BGC823CLDN18.2 xenografts.The tumor uptake reaches(14.59±2.23)％ID/g at 4 h,peaks at(47.73±14.90)％ID/g at 72 h,and exhibits continuous specific retention within 240 h((13.65±3.62)％ID/g).The clearance from blood is relatively fast,and the target-to-non-target ratio increases significantly over time.Micro-SPECT/CT imaging and in vivo pharmacodynamics results demonstrate distinct radioactive accumulation in the tumor lesions starting from 24 h and continuous visualization up to 240 h.A single intravenous injection(18.5 MBq)significantly inhibits tumor growth in tumor-bearing mice without obvious systemic toxicity,further confirming the in vivo targeting specificity and therapeutic efficacy of 177Lu-DOTA-h1D6.The 177Lu-DOTA-h1D6 prepared in this study exhibits good in vitro stability,high in vivo targeting specificity,and significant anti-tumor effects,showing potential application value in the radioimmunotherapy of CLDN18.2-positive tumors.关键词
CLDN18.2/177Lu/放射免疫治疗/单克隆抗体/胃癌Key words
CLDN18.2/177Lu/radioimmunotherapy/monoclonal antibody/gastric cancer分类
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张蕴瀚,王冠哲,耿昊,段菲,肖展雄,成伟华,弓建华..177Lu标记的靶向CLDN18.2放射免疫药物制备及生物学评价[J].原子能科学技术,2026,60(z1):18-28,11.基金项目
中核集团"青年英才"项目 （）
