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CD45单抗介导的淋巴瘤荷瘤裸鼠三步法预定位放免显像 被引量:2

Three-step Pretargeted Radioimmunoimaging in Nude Mice Bearing Human B Cell Lymphoma by CD45 Monoclonal Antibody
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摘要 【目的】评价生物素化CD45单抗介导的99mTc-生物素在人Raji细胞移植瘤裸鼠模型中三步法预定位放免显像的价值。【方法】CD45单抗及DTPA-生物素的99mTc标记采用直接标记法。取人Raji细胞移植瘤裸鼠18只,随机分为2组,每组9只。实验组为三步法预定位放免显像组,静注生物素化CD45单抗100μg,48 h后静注亲和素200μg,再过48 h静注99mTc-生物素7.4 MBq(20μg);对照组为99mTc-CD45单抗放免显像组,静注99mTc-CD45单抗100μg。上述两组裸鼠分别于注药后3、6、12 h分别进行SPECT显像,每个时间点各取3只裸鼠断颈处死后,取脏器组织及肿瘤,称重后在γ计数仪中测量放射性计数,经放射性衰变校正后计算各脏器的%ID/g及肿瘤/非肿瘤(T/NT)比值。【结果】平均每分子CD45单抗约结合12分子生物素,CD45单抗及DTPA-生物素的99mTc标记率分别>70%和>80%。三步法给药后荷瘤裸鼠SPECT显像及生物分布示:整个显像期间血池内放射性均较低,肝脾见较多放射性浓聚;注射标记物后3-6 h,肿瘤显影清晰,并持续到12 h;注药后3、6和12 h肿瘤的%ID/g分别为1.73±0.22、1.24±0.03和0.94±0.07;肿瘤/血液比值分别为3.5、4.9和7.8;肿瘤/肌肉比值分别为8.2、8.9和10.4。而静注99mTc-CD45单抗后则可见肝脾及肾脏明显放射性聚集,12 h血池内见较多放射性分布,肿瘤部位见有少量放射性集聚,12 h肿瘤的%ID/g为0.89±0.13,肿瘤/血液及肿瘤/肌肉的比值分别为1.6和2.5。【结论】与99mTc-CD45单抗相比较,99mTc-生物素三步法预定位放免显像明显改善肿瘤T/NT比值,标记物注射后3 h即可使肿瘤显影。 [ Objective ] To evaluate the value of three-step pretargeting radioimmuno imaging (RII) in nude mice bearing human B cell lymphoma by CD45 monoclonal antibody (mAb). [Methods] The radiolabeling of DTPA-biotin and CD45 rnAb with 99mTc was performed with direct method. 18 nude mice with implanted lymphoma by subcutaneous injection of Raji cells were randomly divided into two groups (9 per group). The first group was the three-step pretargeting RII in which first 100 ug of the biotinyled CD45 mAb was injected, followed by 200 ug avidin and finally received 7.4 MBq (20 ug) of the 99mTc-biotin. Another group was the RII received 7.4 MBq (20 ug) of the 99mTc-CD45 mAb. All nude mice were imaged at 3,6, and 12 h post-injection, and then immediately sacrificed for biodistribution study. The tissue and organ samples were collected, weighed and counted. Uptake of radioactivity in the tumor and normal tissues and organs was expressed as %ID/g and the ratio of tumor to normal tissue. [Results] The labeling ratio of 99mTc-biotin was over 80% and for 99mTc-CD45 mAb over 70%. In group of three-step pretargeting it was showed that there were the some radioactivity depositing in liver and spleen and less radioactivity retention in blood during the whole imaging. However for transplant tumor the tumor was clearly imaged at 3-6 h post-injection. It was also observed that the accumulation of radioactivity in tumor increased as time, and even at 12 h the tumor still be clearly imaged. The %ID/g of tumor at 3, 6, 12 h post-injection was 1.73 ±0.22, 1.24 ± 0.03, and 0.94 ± 0.07, respectively. And the ratios of tumor to blood reached 3.5, 4.9, and 7.8, respectively, while the ratios of tumor to muscle 8.2, 8.9 and 10.4, respectively. However, in group of 99mTc-CD45 mAb the intensive radioactivity depositing in liver, spleen, kidney, blood and less radioactivity accumulation in tumor were observed. The %ID/g of tumor was 0.89 ± 0.13 at 12 h, and the ratios of tumor to blood and tumor to muscle reached 1.6 and 2.5, respectively. [ Conclusions ] Compared to 99mTc-CD45 mAb, three-step pretargeting RU have improved the ratio of tumor to normal tissue. Tumor could be clearly revealed at 3 hr post-injection.
出处 《中山大学学报(医学科学版)》 CAS CSCD 北大核心 2014年第1期127-131,共5页 Journal of Sun Yat-Sen University:Medical Sciences
基金 广东省科技计划项目(2010B060900055) 广州市科技计划项目(2010GN-E00221)
关键词 预定位技术 亲和素-生物素系统 CD45单抗 放射性标记 淋巴瘤 pretargeting technique avidin-biotin system CD45 monoclonal antibody radiolabeling lymphoma
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