摘要
目的 制备特异性整合素αvβ3探针[^18F]氟化铝-匹仑吉肽（^18F-Al-NOTA-PRGD2）,探讨其用于甲状腺乳头状癌（PTC） PET显像的可行性.方法 采用氟化铝新策略制备18F-Al-NOTA-PRGD2.取新鲜切除的人PTC肿瘤组织接种于裸鼠右腋下,制得荷人PTC裸鼠模型.再分别取人PTC标本及毗邻的正常组织、荷瘤裸鼠移植瘤行整合素αvβ3免疫组织化学染色.荷瘤裸鼠（n=5）尾静脉注射1.1 MBq ^18F-Al-NOTA-PRGD2后30、60和120 min分别行microPET显像,通过ROI技术计算肿瘤和主要脏器的放射性摄取值（％ ID/g）,并通过阻断实验验证其特异性.另取15只荷瘤裸鼠研究其注药后30、60及120 min生物分布,计算放射性摄取值（％ID/g）.用两样本t检验进行统计学处理.结果 成功制备^18F-Al-NOTA-PRGD2,标记率＞45％.免疫组织化学染色证实人PTC标本和裸鼠移植瘤组织整合素αvβ3染色均呈棕褐色阳性表达,人PTC毗邻正常组织不表达.荷瘤裸鼠注射^18 F-Al-NOTA-PRGD2后行microPET显像示,肿瘤清晰可见,且与周围组织对比度良好.注射后30、60、120 min肿瘤对显像剂的摄取值分别为（2.81±0.35）、（2.45±0.27）和（1.80±0.21） ％ID/g.PRGD2阻断后,注射^18F-Al-NOTA-PRGD2后60 min肿瘤对显像剂的摄取值降为（0.51±0.05） ％ID/g.荷瘤裸鼠生物分布实验示,注射显像剂后30、60、120 min肿瘤摄取值分别为（3.09±0.25）、（2.75±0.37）和（1.90±0.16） ％ID/g,与microPET显像基本一致（t=1.456、1.465和0.847,均P＞0.05）.^18F-Al-NOTA-PRGD2在血液和肌肉中清除快,注射后60 min肿瘤与血液和肌肉的摄取比值分别为6.15±0.45和7.86±0.56.结论 ^18F-Al-NOTA-PRGD2制备简单,放化纯高,可有效监测PTC中整合素αvβ3表达水平;其PET显像有望为研究PTC整合素αvβ3受体相关机制提供一种新方法.
Objective To prepare a specific integrin αvβ3 probe ^18F-Al-1,4,7-triacetic acid-1,4,7-triazacyclononane-2-（4-amino benzyl） thioamide-（3,6,9-trioxaundecanoic acid-11-amide）-（glutamic acid-cyclo（arginine-glycine-aspartic acid-phenylalanine-lysine） dimeric peptide） （^18 F-Al-NOTA-PRGD2） and evaluate its feasibility for PET imaging in papillary thyroid carcinoma （PTC）.Methods ^18F-Al-NOTA-PRGD2 was synthesized by a novel Al18F complex strategy.Human PTC tissues were implanted into nude mice.Immunohistochemistry staining was performed to detect αvβ3 expression in human PTC tissues,xenografts in mice and adjacent normal tissues respectively.^18F-Al-NOTA-PRGD2 with or without blocking agent of PRGD2 was injected via the tail vein into tumor-bearing mice （n =5） for microPET imaging.The radioactivity uptake in the tumor and major organs were measured via ROI technology.Biodistribution studies were also performed in tumor bearing mice （n=15） 30,60,120 min postinjection respectively.The two sample t test was used for statistical analysis.Results The labeling yield of ^18F-Al-NOTA-PRGD2 was over 45% （no attenuation correction） and the radiochemical purity was above 95%.The integrin αvβ3 expression was observed in human PTC both in situ specimens and xenograft in mice,while no expression was shown in the adjacent normal tissues.MicroPET imaging revealed that tumors were clearly visible with good tumor-to-background contrast.The radioactive uptake by tumor was （2.81 ±0.35） % ID/g,（2.45±0.27） %ID/g and （1.80±0.21） %ID/g at 30,60 and 120 min postinjection,respectively.In the presence of unradiolabeled PRGD2,the corresponding tumor uptake decreased to （0.51±0.05） %ID/g at 60 min postinjection.High tumor uptake was also shown in the biodistribution studies,which was （3.09±0.25） %ID/g,（2.75±0.37） %ID/g and （1.90±0.16） %ID/g at 30,60 and 120 min postinjection,respectively.The results were consistent with the microPET imaging results （t=1.456,1.465 and 0.847,respectively,all P〉0.0.5）.^18F-Al-NOTA-PRGD2 was rapidly cleared in blood and muscles,and the tumor to blood and muscle uptake ratios were 6.15±0.45 and 7.86±0.56 respectively.Conclusions ^18F-Al-NOTA-PRGD2 could be labeled easily and quickly with good labeling yield and radiochemical purity.Overexpressed integrin αvβ3 in PTC can be proved by both immunostaining and microPET imaging.^18F-A1-NOTA-PRGD2 PET imaging might be a novel in vivo method for investigation of molecular mechanism in PTC.
出处
《中华核医学与分子影像杂志》
CSCD
北大核心
2014年第5期374-378,共5页
Chinese Journal of Nuclear Medicine and Molecular Imaging
基金
国家自然科学基金（81171399,81101077）
江苏省科技支撑计划（BE2012622）
江苏省医学重点人才项目（RC2011095）
作者简介
通信作者：杨敏，Email：yangmin@jsinm．org
