基于七甲川菁构建并初步评估双模态PET/近红外荧光探针  

Construction and preliminary evaluation on dual-modal PET/near-infrared fluorescent probe with heptamethine

作　　者：朱家序 蒋亚群 潘芯 李崇佼 雷萍[2] 何勇 ZHU Jiaxu;JIANG Yaqun;PAN Xin;LI Chongjiao;LEI Ping;HE Yong(Department of Nuclear Medicine,Zhongnan Hospital of Wuhan University,Wuhan 430071,China;School of Basic Medicine,Tongji Medical College,Huazhong University of Science and Technology,Wuhan 430030,China)

机构地区：[1]武汉大学中南医院核医学科,湖北武汉430071 [2]华中科技大学同济医学院基础医学院,湖北武汉430030

出　　处：《中国医学影像技术》2023年第5期646-650,共5页Chinese Journal of Medical Imaging Technology

基　　金：国家自然科学基金(82171986)。

摘　　要：目的 基于七甲川菁染料MHI148构建新型PET/近红外荧光(NIRF)双模态探针,并初步评估其用于肿瘤模型小鼠成像的能力。方法 采用双功能螯合剂DOTA修饰MHI148构建MHI148-DOTA,对其光物理、光热性能进行表征;以放射性核素^(68)Ga标记MHI148-DOTA,合成探针^(68)Ga-MHI148,测定其放射化学纯度及稳定性。建立小鼠乳腺癌4T1及人脑胶质母细胞瘤U-87MG皮下瘤模型,以^(68)Ga-MHI148探针对其进行小动物PET显像,观察成像效果及该探针在小鼠体内的生物分布。结果 MHI148-DOTA光物理及光热性能优异。以之构建的探针^(68)Ga-MHI148放射化学纯度>99%,稳定性良好;小动物PET成像可清晰显示肿瘤,肿瘤摄取随时间延长而逐渐升高,6 h时U-87MG及4T1肿瘤/肌肉摄取比值分别为4.55±0.20及8.08±2.26;^(68)Ga-MHI148小鼠体内主要分布于血液、肺、肝及肾脏。结论 成功构建的双模态^(68)Ga-MHI148探针标记简单、稳定性良好,肿瘤靶向潜力较好,并可在近红外激光照射下抑制小鼠肿瘤细胞生长。Objective To construct a novel dual-modal PET/near-infrared fluorescence(NIRF) probe based on heptamethine dye MHI148,and to preliminarily evaluate the imaging capability of this probe for tumor model mice.Methods MHI148 was modified with a bifunctional chelating agent(i.e.DOTA) to synthesize MHI148-DOTA.The photophysical and photothermal properties of MHI148-DOTA were characterized.Then probe ^(68)Ga-MHI148 was prepared by chelating radionuclide ^(68)Ga with MHI148-DOTA,and its radiochemical purity and stability were analyzed.Mice models of breast cancer 4T1 and human glioblastoma U-87MG subcutaneous tumor were established to evaluate the effect of ^(68)Ga-MHI148 probe on micro-PET imaging and its biodistribution in mice.Results MHI148-DOTA had excellent photophysical and photothermal properties.The probe ^(68)Ga-MHI148 was successfully constructed with radiochemical purity over 99% and good stability.Micro-PET scan could clearly show the subcutaneous tumors of mice,and tumor uptake gradually increased with the extension of time.The U-87MG and 4T1 tumor/muscle uptake ratios at 6 h was 4.55±0.20 and 8.08±2.26,respectively.^(68)Ga-MHI148 mainly distributed in blood,lung,liver and kidney of mice.Conclusion A dual-modal ^(68)Ga-MHI148 probe was successfully constructed,which was simple to label and stable with good tumor targeting potential,and might inhibit the growth of tumor cells under near-infrared laser in mice.

关 键 词：分子探针技术 七甲川菁 镓 正电子发射断层显像 谱学 近红外线 

分 类 号：R73[医药卫生—肿瘤] R817[医药卫生—临床医学]