18F-阿法肽荷瘤裸鼠模型显像与药代动力学研究

摘要

Objective To assess the imaging characteristics of 18F-Alfalide II in different tumorbearing mice and pharmacokinetics in Beagle dogs.Methods BALB/c nude mice(n-24)were used for subcutaneous tumor models(A549 and U87MG),orthotopic lung cancer models(A549)and orthotopic breast cancer models(MDA-MB-231)(n=6 in each group).18F-Alfatide II and 18F-fluorodeoxyglucose(FDG)microPET/CT images were compared in the 4 types of tumor-bearing nude mice models.18F-Alfatide II blocking experiment,biodistribution experiment and imaging studies in tumors of different growth cycles were performed in A549 subcutaneous tumor-bearing nude mice models.Pharmacokinetic experiments were carried out in Beagle dogs(n = 6)and CD-1 mice(n = 9).Two-sample t test was used to analyze the data.Results Compared with 18F-FDG,18F-Alfatide II microPET/CT images showed better imaging quality and contrast in subcutaneous A549,U87MG tumors and orthotopic A549(tumor/heart:4.50±1.17 vs 0.95±0.31;t = 4.125,P<0.01),orthotopic MDA-MB-231(tumor/muscle:6.60±1.53 vs 0.92±0.43;t = 3.984,P<0.01)transplantation nude mice models.18F-Alfatide II could specifically target A549 tumors,and the tumor uptake of 18F-Alfatide II was reduced by about 75% after pre-injection with cyclo(Arg-Gly-Asp-D-Tyr-Lys)(c(RGDyk)).18F-Alfatide II was rapidly cleared from the blood of Beagle dogs(T1/2 was(57.34±11.69)min).It was cleared in the form of prototype drug and(69.24±6.82)% of cumulative dose was excreted through the urine within 4 h after administration.Conclusions 18F-Alfatide II shows a higher targeton-target ratio than,18F-FDG in the imaging of A549,MDA-MB-231 and U87MG tumor-bearing nude mice models,which is more conducive to the diagnosis of tumor.18F-Alfatide II has excellent pharmacokinetic properties.%目的 探讨18F-阿法肽(18F-Alfatide II)在不同荷瘤裸鼠模型中的显像及Beagle犬中的药代动力学性能.方法 取BALB/c裸鼠24只,分别制备皮下荷瘤裸鼠模型(肺癌A549和神经胶质瘤U87MG)、原位肺癌模型(A549)和原位乳腺癌模型(MDA-MB-231)各6只.于4种荷瘤裸鼠模型中行18F-Aifatide II与18F-脱氧葡萄糖(FDG)对比显像;于A549皮下荷瘤裸鼠模型中行18F-Alfatide II阻断 实验、生物分布实验及在不同生长周期肿瘤中的显像研究;于Beagle犬(6只)及CD-I小鼠(9只)中行 药代动力学实验.采用两样本t检验分析数据.结果 与18F-FDG相比,18F-Alfatide II在A549、U87MG皮下肿瘤及A549原位肺癌(肿瘤/心脏比值,4.50±1.17与0.95±0.31;t = 4.125,P<0.01)、MDA-MB-231原位乳腺癌(肿瘤/肌肉比值,6.60±1.53与0.92±0.43;t = 3.984,P<0.01)荷瘤裸鼠模型中有更 好的显像质量.预先注射阻断剂环(精氨酸-甘氨酸-天冬氨酸-D-酪氨酸-赖氨酸多肽[c(RGDyk)]后,A549肿瘤对18F-Alfatide II的摄取降低了 75%,F-Alfatide II在Beagle犬血液中快速清除,半衰期为(57.34±11.69)min.18F-Alfatide II以原药形式从体内快速清除,给药后4 h内,(69.24±6.82)%的给药剂量通过尿液排出.结论 18F-Alfatide II在A549、MDA-MB-231、U87MG肿瘤显像的靶/非靶比值高于18 F-FDG,可显著提高显像质量,且药代动力学性能优良.