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目的探讨~(99)Tc~m 直接标记带有10个连续组氨酸的膜联蛋白 V(Annexin V)衍生物的可行性,研究其在健康小鼠体内的分布和肺癌裸鼠模型凋亡显像。方法直接标记法制备~(99)Tc~m-Annexin V 衍生物,并测产物放化纯、胶体含量及健康小鼠体内不同时间点(5,30 min 和1,2,4,6,12,24 h)的生物分布,DAS 2.0软件拟合计算药代动力学参数。建立荷 H460非小细胞肺癌裸鼠模型,分为紫杉醇诱导化疗组(5只)和未治疗对照组(5只)。紫杉醇诱导化疗后48 h,于裸鼠尾静脉注射~(99)Tc~m-Annexin V 衍生物18.5 MBq,2和4 h 时进行凋亡显像,勾画 ROI 并计算肿瘤与对侧正常组织(T/NT)放射性比值。结果放化纯达(98.01±1.67)%,3 h 后放化纯仍可达(95.45±1.34)%,胶体含量为(3.31±1.37)%。健康小鼠体内分布实验表明肾脏对该示踪剂摄取最高,肝、脾摄取较少。DAS 2.0软件拟合得到时间-放射性曲线符合二室模型特征,分布相半衰期(T_(1/2α))为(21.18±5.95)min,清除相半衰期(T_(1/2β))为(69.32±0.10)min。荷瘤鼠显像示,给药后2 h 即可获得清晰的图像,紫杉醇诱导化疗组2和4 h 的 T/NT 比值为3.85±1.10和4.63±0.97,明显高于对照组(1.60±0.29和1.71±0.43,P<0.01)。结论该Annexin V 衍生物易于~(99)Tc~m直接标记,方法简便,标记物在血液中清除迅速,肝、脾摄取少,易得到高清晰图像。
Objective To investigate the feasibility of ~ (99) Tc ~ m direct labeling of Annexin V derivatives with 10 consecutive histidines to study their distribution in healthy mice and apoptosis in nude mice models of lung cancer Imaging. Methods The (99) Tc m-Annexin V derivatives were prepared by direct labeling method, and the radiolabeled pure and colloidal contents of the products were determined at different time points (5,30 min and 1,2,4,6,12 , 24 h), and the DAS 2.0 software fitted the pharmacokinetic parameters. To establish a model of H460 non-small cell lung cancer in nude mice, which was divided into paclitaxel-induced chemotherapy group (n = 5) and untreated control group (n = 5). Forty-eight hours after induction of paclitaxel, apoptotic imaging was performed at a dose of 18.5 MBq ~ (99) Tc ~ m-Annexin V derivatives in the tail vein of nude mice at 2 h and 4 h after radiotherapy. ROI was plotted and tumor and contralateral normal tissues T / NT) radioactivity ratio. The results showed that the radiochemical purity was (98.01 ± 1.67)% pure and reached to (95.45 ± 1.34)% after 3 h. The colloid content was (3.31 ± 1.37)%. In vivo distribution experiments in healthy mice showed that the kidney uptake of the tracer highest, liver, spleen uptake less. DAS 2.0 software fitted the two-compartment model and the half-life (T 1 / 2α) was 21.18 ± 5.95 min and the phase half-life was 69.32 ± 0.10) min. Tumor bearing mice showed that clear images were obtained 2 h after administration. The T / NT ratios at 3 and 4 h after paclitaxel-induced chemotherapy were 3.85 ± 1.10 and 4.63 ± 0.97, significantly higher than those in the control group (1.60 ± 0.29 And 1.71 ± 0.43, P <0.01). Conclusion The Annexin V derivative is easy to direct labeling with ~ (99) Tc ~ m. The method is simple, the marker is rapidly cleared in the blood, the liver and spleen are less ingested, and the high definition image is easy to obtain.