99mTc-GE11分子探针在荷人肺腺癌裸鼠体内分布及受体显像研究  

Biodistribution of 99mTc-GE11 molecular probe and receptor imaging in nude mice bearing lung adenocarcinoma

作　　者：谭祖稳 吴梦雪 李运洁 雷成明[1] 邓婕 段东[1] TAN Zuwen;WU Mengxue;LI Yunjie;LEI Chengming;DENG Jie;DUAN Dong(Department of Nuclear Medicine,the First Affiliated Hospital of Chongqing Medical University,Chongqing,400016,China)

机构地区：[1]重庆医科大学附属第一医院核医学科

出　　处：《第三军医大学学报》2019年第14期1350-1356,共7页Journal of Third Military Medical University

基　　金：重庆市自然科学基金面上项目(CSTC2014jcyjA10012)~~

摘　　要：目的制备靶向肺腺癌细胞跨膜表达蛋白表皮生长因子受体(epidermal growth factor receptor,EGFR)的核素分子探针99mTc-GE11,鉴定其理化性质并探讨其在荷瘤裸鼠体内分布及显像情况。方法采用氯化亚锡氧化还原法对GE11进行99mTc标记,初步鉴定其标记率、比活度、放化纯度及稳定性等,并观察多肽标记物在荷瘤裸鼠体内的生物分布及显像情况。结果 99mTc-GE11标记率为(93.12±0.83)%,比活度为(24.21±0.42)TBq/mmol。体外室温放置6、12 h后,其放化纯度仅下降了2.14%、3.11%。Sephadex G50柱层析后,其与血浆蛋白结合率为4.8%;与不同浓度半胱氨酸37℃温育1 h后,未结合99mTc含量无明显变化;脂/水分配系数lgP为(-1.87±0.05);荷瘤裸鼠体内生物分布及SPECT显像示:99mTc-GE11在血液、肾脏中的放射性清除迅速,肿瘤组织可以选择性浓聚99mTc-GE11,在注射1.0 h时,肿瘤/肌肉比值达到最大,且肿瘤组织显影最清晰。结论制备的99mTc-GE11小分子多肽探针理化特性理想,在荷人肺腺癌裸鼠模型中显像较好。Objective To prepare a 99 mTc-labled molecular probe(99 mTc-GE11) targeting epidermal growth factor receptor(EGFR) on lung adenocarcinoma cells and evaluate its biodistribution and performance for EGFR imaging in nude mice bearing lung adenocarcinoma xenografts. Methods GE11 was labeled with 99 mTc through oxidation and reduction of stannous chloride, and the labeling rate, specific activity, radiochemical purity and stability of 99 mTc-GE11 were assessed. The biodistribution profile and receptor imaging performance of 99 mTc-GE11 were evaluated in a nude mouse model bearing lung adenocarcinoma xenografts. Results The mean labeling rate of 99 mTC-GE11 was(93.12±1.43)%, and its mean specific activity was 24.21±0.42 TBq/mmol. At room temperature, the radiochemical purity of 99 mTC-GE11 was reduced by 2.14% at 6 h and by 3.11% at 12 h. The results of chromatography with Sephadex-G50 column showed that the binding rate of 99 mTC-GE11 with plasma proteins was 4.8%. At 37 ℃, incubation of 99 mTc-GE11 with different concentrations of cysteine for 1 h did not cause significant changes in the level of free 99 mTc. The fat/water distribution coefficient(lgP) of 99 mTC-GE11 was-1.87±0.05. In the tumor-bearing nude mice, 99 mTc-GE11 was rapidly cleared in blood and kidney after intravenous injection and was selectively accumulated in the tumor;the tumor/non-tumor(T/NT) ratio reached the highest level and the clearest tumor imaging was achieved at 1 h after the injection. Conclusion 99 mTc-GE11 molecular probe prepared based on a small molecular polypeptide possesses good physiochemical properties with an optimal biodistribution profile, and allows clear in vivo tumor imaging in tumor-bearing nude mice.

关 键 词：肺腺癌 表皮生长因子受体 多肽 GE11 核素分子探针 

分 类 号：R734.2[医药卫生—肿瘤] R817-33[医药卫生—临床医学]