本文關(guān)鍵詞： 多肽 锝 肺癌 同位素標(biāo)記 藥代動力學(xué)　出處：《蘇州大學(xué)》2016年博士論文　論文類型：學(xué)位論文

【摘要】：目的：探索99Tcm-精氨酸-谷氨酸-蘇氨酸(99Tcm-Arg-Glu-Thr,99Tcm-RET)和99Tcm-精氨酸-谷氨酸-甘氨酸(99Tcm-Arg-Glu-Gly,99Tcm-REG)的放射性核素標(biāo)記方法,探索99Tcm-RET和99Tcm-REG的穩(wěn)定性,并研究與荷人肺癌A549和H1299細(xì)胞結(jié)合率的影響因素,觀察其在正常小鼠和荷肺癌裸鼠體內(nèi)的生物學(xué)分布情況,探討其用于肺癌顯像的可行性。方法：采用99Tcm直接法標(biāo)記標(biāo)記三肽RET和REG,行99Tcm-RET和99Tcm-REG與A549和H1299細(xì)胞結(jié)合實(shí)驗(yàn)。正常小鼠尾靜脈注射99Tcm-RET或99Tcm-REG后不同時間處死,取主要臟器或組織,測定其每克組織的放射性百分注射劑量率(%ID/g)。另取尾靜脈注射99Tcm-RET和99Tcm-REG后不同時間小鼠血液,測量放射性計(jì)數(shù)并計(jì)算藥代動力學(xué)參數(shù)。行尾靜脈注射99Tcm-RET和99Tcm-REG后,荷人肺癌H1299裸鼠不同時間SPECT顯像。結(jié)果：99Tcm-RET的標(biāo)記率為(93.15±2.02)%,放置入人新鮮血清中1,2,4,6,24h后,99mTc-RET放射化學(xué)純度分別為(92.18±1.51)%,(92.00±1.41)%,(91.30±1.67)%,(90.78±2.48)%和(90.65±0.60)%。最優(yōu)標(biāo)記條件下99Tcm-REG的標(biāo)記率為(92.90±2.86)%,放置入人新鮮血清中1、2、4、6和24 h后,99Tcm-REG放射化學(xué)純度分別為(91.43±1.14)%、(91.50±1.28)%、(91.05±2.60)%、(90.53±3.00)%和(89.15 ± 1.57)%。99Tcm-REG與非小細(xì)胞肺癌細(xì)胞A549和H1299的最高特異性結(jié)合率分別為(1.29±0.16)%和(2.32±0.31)%。99Tcm-RET與非小細(xì)胞肺癌細(xì)胞A549和H1299的最高特異性結(jié)合率分別為(3.78±0.29)%和(3.56±0.37)%。體內(nèi)分布提示99Tcm-REG在小鼠血液中清除迅速,2h時放射性僅為注射5min時的20.26%,此時體內(nèi)分布研究示腫瘤%ID/g為1.95±0.73,腫瘤/肌肉的放射性計(jì)數(shù)比值(T／NT)為3.50±1.27。肝臟、脾臟有較多放射性攝取,且呈緩慢下降,腎臟、心、肺放射性攝取隨時間逐漸下降,其余組織放射性呈低水平。尾靜脈注射99Tcm-RET后4h荷瘤裸鼠顯像示腫瘤顯影清晰,此時體內(nèi)分布研究示腫瘤%ID/g達(dá)4.96±1.05,肝臟、脾臟有較多放射性攝取,而心臟和血液內(nèi)放射性攝取較少。腫瘤與心臟和血液的放射性計(jì)數(shù)比值(T/NT)最高可達(dá)5.7±0.21和12.4±0.11。結(jié)論：99Tcm-RET和99Tcm-REG易于制備,99Tcm-RET對肺癌細(xì)胞H1299的親和力較99Tcm-REG高,具有較理想的動物體內(nèi)動力學(xué),對腫瘤的高親和性,具有潛在的新型靶向性顯像藥物,有可能成為一種親肺癌腫瘤顯像劑。
[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 鹵2.02g and placed in human fresh serum. The radiochemical purity of 99mTc-RET was 92. 18 鹵1. 51% and 92. 00 鹵1. 41% respectively. 90.78 鹵2.48% and 90.65 鹵0.60% respectively. The labeling rate of 99Tcm-REG was 92.90 鹵2.86% under the optimal labeling conditions. The radiochemical purity of 99Tcm-REG in fresh serum was 91.43 鹵1.14 and 91.50 鹵1.28%, respectively. 91.05 鹵2.60%. 90.53 鹵3.00% and 89.15 鹵1.57). The highest specific binding rates of 99Tcm-REG to NSCLC cells A549 and H1299 were 1.29 鹵0.16% and 2.32 鹵0.31, respectively. The highest specific binding rates of 0.99Tcm-RET to A549 and H1299 cells were 3.78 鹵0.29% and 3.56 鹵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 鹵0.73. The radioactivity count ratio of tumor to muscle was 3.50 鹵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 鹵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 鹵0.21 and 12.4 鹵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.
【學(xué)位授予單位】：蘇州大學(xué)
【學(xué)位級別】：博士
【學(xué)位授予年份】：2016
【分類號】：R734.2;R730.44

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