放射性核素标记三肽RET和REG在肺癌分子显像中的实验研究

发布时间：2018-01-22 22:12

本文关键词： 多肽锝肺癌同位素标记药代动力学　出处：《苏州大学》2016年博士论文　论文类型：学位论文

【摘要】：目的：探索99Tcm-精氨酸-谷氨酸-苏氨酸(99Tcm-Arg-Glu-Thr,99Tcm-RET)和99Tcm-精氨酸-谷氨酸-甘氨酸(99Tcm-Arg-Glu-Gly,99Tcm-REG)的放射性核素标记方法,探索99Tcm-RET和99Tcm-REG的稳定性,并研究与荷人肺癌A549和H1299细胞结合率的影响因素,观察其在正常小鼠和荷肺癌裸鼠体内的生物学分布情况,探讨其用于肺癌显像的可行性。方法：采用99Tcm直接法标记标记三肽RET和REG,行99Tcm-RET和99Tcm-REG与A549和H1299细胞结合实验。正常小鼠尾静脉注射99Tcm-RET或99Tcm-REG后不同时间处死,取主要脏器或组织,测定其每克组织的放射性百分注射剂量率(%ID/g)。另取尾静脉注射99Tcm-RET和99Tcm-REG后不同时间小鼠血液,测量放射性计数并计算药代动力学参数。行尾静脉注射99Tcm-RET和99Tcm-REG后,荷人肺癌H1299裸鼠不同时间SPECT显像。结果：99Tcm-RET的标记率为(93.15±2.02)%,放置入人新鲜血清中1,2,4,6,24h后,99mTc-RET放射化学纯度分别为(92.18±1.51)%,(92.00±1.41)%,(91.30±1.67)%,(90.78±2.48)%和(90.65±0.60)%。最优标记条件下99Tcm-REG的标记率为(92.90±2.86)%,放置入人新鲜血清中1、2、4、6和24 h后,99Tcm-REG放射化学纯度分别为(91.43±1.14)%、(91.50±1.28)%、(91.05±2.60)%、(90.53±3.00)%和(89.15 ± 1.57)%。99Tcm-REG与非小细胞肺癌细胞A549和H1299的最高特异性结合率分别为(1.29±0.16)%和(2.32±0.31)%。99Tcm-RET与非小细胞肺癌细胞A549和H1299的最高特异性结合率分别为(3.78±0.29)%和(3.56±0.37)%。体内分布提示99Tcm-REG在小鼠血液中清除迅速,2h时放射性仅为注射5min时的20.26%,此时体内分布研究示肿瘤%ID/g为1.95±0.73,肿瘤/肌肉的放射性计数比值(T／NT)为3.50±1.27。肝脏、脾脏有较多放射性摄取,且呈缓慢下降,肾脏、心、肺放射性摄取随时间逐渐下降,其余组织放射性呈低水平。尾静脉注射99Tcm-RET后4h荷瘤裸鼠显像示肿瘤显影清晰,此时体内分布研究示肿瘤%ID/g达4.96±1.05,肝脏、脾脏有较多放射性摄取,而心脏和血液内放射性摄取较少。肿瘤与心脏和血液的放射性计数比值(T/NT)最高可达5.7±0.21和12.4±0.11。结论：99Tcm-RET和99Tcm-REG易于制备,99Tcm-RET对肺癌细胞H1299的亲和力较99Tcm-REG高,具有较理想的动物体内动力学,对肿瘤的高亲和性,具有潜在的新型靶向性显像药物,有可能成为一种亲肺癌肿瘤显像剂。
[Abstract]:Objective: to explore 99Tcm-Arg-Glu-Thr (99Tcm-Arg-Glu-Thr). 99Tcm-RET) and 99Tcm-Arg-Glu-Glyn 99Tcm-REG) were labeled by radionuclides. To explore the stability of 99Tcm-RET and 99Tcm-REG, and to study the factors influencing the binding rate of human lung cancer A549 and H1299 cells. To observe its biological distribution in normal mice and nude mice bearing lung cancer, and to explore the feasibility of its application in lung cancer imaging. Methods: RET and REG were labeled with 99Tcm direct method. The binding test of 99Tcm-RET and 99Tcm-REG to A549 and H1299 cells was performed. Normal mice were injected with 99Tcm-RET or 99Tcm-REG at different times after injection of 99Tcm-RET or 99Tcm-REG. To be executed. Take the main organs or tissues. The radioactivity percent injection dose rate per gram of tissue was measured and the blood samples of mice were taken after injection of 99Tcm-RET and 99Tcm-REG into caudal vein at different times after injection of 99Tcm-RET and 99Tcm-REG. Radioactivity counts were measured and pharmacokinetic parameters were calculated. 99Tcm-RET and 99Tcm-REG were injected via caudal vein. Results the labeling rate of 10% 99Tcm-RET was 93.15 卤2.02g and placed in human fresh serum. The radiochemical purity of 99mTc-RET was 92. 18 卤1. 51% and 92. 00 卤1. 41% respectively. 90.78 卤2.48% and 90.65 卤0.60% respectively. The labeling rate of 99Tcm-REG was 92.90 卤2.86% under the optimal labeling conditions. The radiochemical purity of 99Tcm-REG in fresh serum was 91.43 卤1.14 and 91.50 卤1.28%, respectively. 91.05 卤2.60%. 90.53 卤3.00% and 89.15 卤1.57). The highest specific binding rates of 99Tcm-REG to NSCLC cells A549 and H1299 were 1.29 卤0.16% and 2.32 卤0.31, respectively. The highest specific binding rates of 0.99Tcm-RET to A549 and H1299 cells were 3.78 卤0.29% and 3.56 卤0.37, respectively. The distribution of 99Tcm-REG in vivo indicated that 99Tcm-REG was cleared rapidly in the blood of mice. The radioactivity at 2 h was 20.26% of that at 5 min after injection. The in vivo distribution of the tumor showed that the ID / P g of the tumor was 1.95 卤0.73. The radioactivity count ratio of tumor to muscle was 3.50 卤1.27.The liver, spleen and spleen had more radioactivity uptake, and the kidney, heart and lung radioactivity uptake decreased gradually with time. The radioactivity of other tissues was low. 4 h after injection of 99Tcm-RET, the imaging showed that the tumor showed clear development in nude mice, and the distribution in vivo showed that the tumor ID-g was 4.96 卤1.05. Liver and spleen have more radioactivity. The radioactivity in the heart and blood is less. The ratio of radioactivity of tumor to heart and blood is T / NT. The highest values were 5.7 卤0.21 and 12.4 卤0.11.Conclusion: 1. 99Tcm-RET and 99Tcm-REG are easy to be prepared. The affinity of 99Tcm-RET to lung cancer cell H1299 was higher than that of 99Tcm-REG. It may become a tumor imaging agent for lung cancer because of its potential new target imaging drugs.
【学位授予单位】：苏州大学
【学位级别】：博士
【学位授予年份】：2016
【分类号】：R734.2;R730.44

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