摘要
L型氨基酸转运蛋白(LAT1)作为癌症显像与治疗的靶点,是目前癌症研究的热点之一。本研究以4-硼-L-苯丙氨酸(BPA)为反应物,采用水相一步放射取代反应合成^(131)I标记的4-碘-L-苯丙氨酸(^(131)IPA)示踪剂,并进行肿瘤诊断研究的初步评估。结果显示,所合成的^(131)IPA放射化学纯度(RCP)为96.33%,放射化学产率(RCY)达到92%±0.3%。非小细胞肺癌A549细胞对^(131)IPA的摄取量在3 h达到最高;而胶质瘤GL261细胞对其的摄取量在8 h达到峰值。在小鼠体内^(131)IPA主要通过肝、肾代谢及排泄,24 h后体内几乎无残留。此外,小动物活体成像显示2~12 h内^(131)IPA在A549肿瘤模型中具有高的摄取量和较长的停留时间,在原位GL261肿瘤模型中2 h可观察到^(131)IPA透过血脑屏障到达脑肿瘤,8 h及12 h成像显示其有较好的脑肿瘤特异性,靶本比为T/M≈3.4。
L-type amino acid transporter protein(LAT1)is one of the hotspots in cancer research as a target for cancer visualization and therapy.In this study,^(131)I-labeled 4-iodo-L-phenylalanine(^(131)IPA)tracer was synthesized by aqueous-phase onestep radiosubstitution reaction using 4-boron-L-phenylalanine(BPA)as a reactant and initially evaluated for tumor diagnostic studies.The results showed that the radiochemical purity(RCP)of the synthesized^(131)IPA was 96.33%,and the radiochemical yield(RCY)reached 92±0.3%.The intake of^(131)IPA in non-small-cell lung cancer A549 cells reached the highest value at 3 h;whereas the intake in glioma GL261 cell to peak value was at 8 h.In mice,^(131)IPA was mainly metabolized and excreted through the liver and kidney,with almost no residue in the body after 24 h.In addition,in vivo imaging in small animals showed that^(131)IPA had high intake and long residence time in A549 tumor model from 2 to 12 h.In the in situ GL261 tumor model,^(131)IPA could be observed to reach brain tumors through the blood-brain barrier at 2 h.Imagings at 8 h and 12 h showed better brain tumor specificity,with a target-to-benefit ratio of T/M≈3.4.
作者
马言熙
程伟
高菲妃
原凌燕
邴志桐
甘露
俞博毅
崔振存
李永昊
柳江燕
马建苹
陈卫强
MA Yanxi;CHENG Wei;GAO Feifei;YUAN Lingyan;BING Zhitong;GAN Lu;YU Boyi;CUI Zhencun;LI Yonghao;LIU Jiangyan;MA Jianpin;CHEN Weiqiang(School of Life Science and Engineering,Lanzhou University of Technology,Lanzhou 730050,China;Institute of Modern Physics,Chinese Academy of Sciences,Lanzhou 730000,China;Guangdong Provincial Laboratory of Advanced Energy Science and Technology,Huizhou 516000,Guangdong,China;School of Nuclear Science and Technology,University of Chinese Academy of Sciences,Beijing 100049,China;School of Life Sciences,University of Chinese Academy of Sciences,Beijing 100049,China;Department of Nuclear Medicine,The Second Hospital of Lanzhou University,Lanzhou 730030,China)
出处
《原子核物理评论》
北大核心
2025年第2期356-364,共9页
Nuclear Physics Review
基金
甘肃省自然基金基础研究创新群体项目(23JRRA569)。
