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高剂量的PET显像剂18F-FDG对小鼠大肠癌肿瘤模型治疗效果的实验研究

Experimental Study on Therapeutic Effect of Positron Emission Tomography Agent 18F-FDG in a Colon Cancer Mouse Model

【作者】 方圣伟

【导师】 张宏;

【作者基本信息】 浙江大学 , 影像医学与核医学, 2010, 硕士

【摘要】 目的:大肠癌是目前发病率最高肿瘤中之一,在男性和女性中大肠癌的发生率和死亡率都很高。现在有很多种放射性核素已应用到大肠癌的综合辅助治疗中,但是应用正电子药物来治疗大肠肿癌的研究至今还没有。理论上来说,正电子也可以像负电子一样杀死肿瘤细胞。本研究就是应用正电子药物18F-FDG来治疗小鼠的大肠癌肿瘤模型并监测治疗效果。方法:在12只裸鼠上建立大肠肿癌模型,把建好肿癌模型的裸鼠随机分成4组,其中一组为对照组不予任何治疗,另外三组分别给1.5mCi、3.0mCi、6.0mCi的18F-FDG治疗。治疗后每周用18F-FDG microPET监测治疗效果,并测量肿瘤的生长率。最后用免疫组化染色检测肿瘤、大脑、心脏、和肾脏葡萄糖转运体和VEGF的表达,用TUNEL方法检测肿瘤、大脑、心脏、和肾脏细胞的凋亡情况。结果:所有治疗组裸鼠肿瘤生长率以及FDG标准摄取都显著低于对照组(p<0.05)。虽然在三个治疗组之间肿瘤生长率以及FDG标准摄取没有显著区别,但是还是可以看到治疗剂量越高,疗效越好。免疫组化染色显示肿瘤组织较大脑、心脏、和肾脏表达更高的葡萄糖转运体和VEGF。治疗组肿瘤细胞凋亡数量显著高于对照组(p<0.05)。结论:本研究表明来源于显像剂18F-FDG的正电子对小鼠大肠癌肿瘤模有一定的治疗效果,提示高剂量的18F-FDG释放出来的正电子可以用于大肠癌以及其它肿瘤的放射治疗。

【Abstract】 Purpose: Colorectal cancer is the third most common cancer in the world, andremains a major cause of cancer death in men and women. Several radionuclides havebeen tried for the treatment of colorectal cancer, but the therapeutic potential ofpositrons has remained unexplored in this type of cancer. Theoretically, positronsshould kill cancer cells as electrons. This study assessed the therapeutic potential ofPET agent [18F] labeled 2-deoxy-2-fluoro-D-glucose (18F-FDG) in a colon cancermouse model.Methods: Colonic adenocarcinoma cells were inoculated in nude mice forestablishing tumor model. Twelve tumor-bearing mice were divided into four groups.Three groups were treated with 1.5 mCi, 3.0 mCi and 6.0 mCi of 18F-FDG, respectively.Control group has not received any treatment. Mice were imaged by microPET with18F-FDG before and after treatment weekly and the tumor growth rate was calculated.Tumor, brain, heart and kidney of mice were analyzed for expression of glucosetransporters and VEGF by immunofluorescent staining, and the presences of apoptosiswere detected by TUNEL method. Results: All three treated groups showed significant 18F-FDG reduction comparedwith the control group (p<0.05). The higher treatment dose, the better treatmentresponse was observed, though there were no significant differences between the threetreated groups. The tumor growth rate of all three treated groups was also significantlydecreased after treatment (p<0.05). There was no significant difference of FDG tumoruptake and growth rate of tumor between treated groups (p>0.05).Immunohistochemistry showed that tumors expressed more glucose transporters thanin brain, heart and kidney. The 18F-FDG treatment of mice resulted in apoptotic celldeath in all three treated groups, which showed significant higher apoptotic cells thancontrol group (p<0.05).Conclusion: The study suggested that positrons delivered by 18F-FDG have atherapuetic effect in colonic cancer animal model, which indicated the potential for thedevelopment of positron emitted therapy with 18F-FDG for colonic cancer and othercancers.

【关键词】 18F-FDG正电子核素治疗大肠癌microPET
【Key words】 18F-FDGpositronradionuclide therapycolon cancermicroPET
  • 【网络出版投稿人】 浙江大学
  • 【网络出版年期】2010年 08期
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