^(131)Ⅰ标记的肝癌核酸适配子在荷瘤裸鼠体内生物分布及显像  

Biodistribution and imaging of ^(131)Ⅰ-labelled hepatoma aptamer in tumor-bearing nude mice

作　　者：杨敏[1] 黄文山 查悦明 张桂雄 许杰华[1] Yang Min;Huang Wenshan;Zha Yueming;Zhang Guixiong;Xu Jiehua(Department of Nuclear Medicine,the Third AffiliatedHospital of Sun Yat-sen University,Guangzhou 510630,China)

机构地区：[1]中山大学附属第三医院核医学科,广州510630

出　　处：《中华肝脏外科手术学电子杂志》2019年第3期260-264,共5页Chinese Journal of Hepatic Surgery(Electronic Edition)

基　　金：国家自然科学基金(81101866);教育部归国留学人员科研启动基金(教外司留[2015]1098号);广东省自然科学基金(2018A030313200);广东省科技计划项目(2014A020212581)

摘　　要：目的探讨^(131)Ⅰ标记肝癌核酸适配子JHIT2(^(131)Ⅰ-JHIT2)作为肝癌靶向显像新型分子探针的可行性。方法采用Ⅰodogen法制备^(131)Ⅰ-JHIT2,纸层析法测标记率及放射化学纯度(放化纯度),检测其在不同溶液中不同时间的放化纯度。采用γ计数器分别测定131I-JHIT2与人肝癌细胞HepG2、正常肝细胞L02结合后细胞的放射性计数。HepG2荷瘤裸鼠尾静脉注射约0.74 MBq^(131)Ⅰ-JHIT2后不同时间处死,测定并计算各脏器每克组织放射性摄取值、肿瘤/肌肉(T/M)放射性比值。荷瘤裸鼠尾静脉注射约9.25 MBq ^(131)Ⅰ-JHIT2后单光子发射计算机断层成像术(SPECT)-CT显像,观察并计算不同时间肿瘤/非肿瘤(T/NT)比值。两种细胞放射性计数比较采用t检验。结果^(131)Ⅰ-JHIT2标记率为(67.8±0.5)%,纯化后放化纯度为(91.4±1.1)%。室温下^(131)Ⅰ-JHIT2在PBS、生理盐水24 h的放化纯度均>80%。^(131)Ⅰ-JHIT2分别与两种细胞结合后,HepG2细胞的放射性计数为(415±9)CPM,明显高于L02细胞的(288±7)CPM(t=15.3,P<0.05)。尾静脉注射^(131)Ⅰ-JHIT2后,荷瘤鼠体内30 min、2 h肿瘤部位每克组织放射性摄取值分别为(4.17±2.83)、(2.22±0.64)%ID/g,T/M比值相应为2.01±1.15、2.07±0.82。SPECT-CT显像示,荷瘤裸鼠注射^(131)Ⅰ-JHIT2后30 min,肿瘤部位可见放射性摄取,T/NT比值为2.63;2 h放射性减低,T/NT比值为1.82。结论 ^(131)Ⅰ-JHIT2探针在体外稳定性较好,对体外HepG2细胞及HepG2细胞荷瘤裸鼠模型具有一定靶向作用,为肝癌靶向核素诊疗奠定一定的基础。Objective To investigate the feasibility of 131I-labeled hepatoma aptamer JHIT2 (131I-JHIT2) as a novel molecular probe for hepatoma-targeted imaging. Methods The 131I-JHIT2 was prepared by Iodogen method. The labeling rate and radiochemical purity were measured by paper chromatography. The radiochemical purity of 131I-JHIT2 was detected in different solutions at different time points. The radioactivity count of 131I-JHIT2 after combining with human hepatoma HepG2 and normal liver cell L02 was measured by gamma counter. The HepG2 tumor-bearing nude mice were sacrificed at different time points after caudal venous injection of approximately 0.74 MBq 131I-JHIT2. The percentage of radioactivity uptake value and tumor/muscle (T/M) radioactivity ratio per 1 g tissues of each organ were measured and calculated. Single-photon emission computed tomography (SPECT)-CT imaging was performed after caudal venous injection of approximately 9.25 MBq 131I-JHIT2 in tumor-bearing nude mice. The tumor/non-tumor (T/NT) ratio was observed and measured at different time points. The radioactive count was statistically compared between two types of cells by t test. Results The labeling rate of 131I-JHIT2 was (67.8±0.5)%, and the radiochemical purity after purification was (91.4±1.1)%. The radiochemical purity of 131I-JHIT2 in PBS or normal saline at room temperature for 24 h was both above 80%. After 131I-JHIT2 combining with two types of cells, the radioactive count of HepG2 cells was (415±9) CPM, significantly higher than (288±7) CPM of L02 cells (t=15.3, P<0.05). At 30 min and 2 h after caudal venous injection of 131I-JHIT2, the percentage of radioactivity uptake value per 1 g tumor tissue in tumor-bearing mice was (4.17±2.83) and (2.22±0.64)%ID/g, and the T/M ratio was 2.01±1.15 and 2.07±0.82. SPECT-CT imaging demonstrated that radioactive uptake was observed at the tumor site in tumor-bearing nude mice and the T/NT ratio was 2.63 at 30 min after 131I-JHIT2 injection. The radioactivity decreased at 2 h, and the T/NT ratio wa

关 键 词：癌 肝细胞 适配子 放射性核素显像 

分 类 号：R735.7[医药卫生—肿瘤]