凋亡显像早期检测肿瘤化疗疗效的实验研究  

Early detection of tumor response to chemotherapy by molecular apoptosis imaging:An experimental study

作　　者：柳曦[1] 张宝石[1] 周乃康[1] 王卉[2] 张晓军[2] 刘健[2] 田嘉禾[2] 张锦明[2] 

机构地区：[1]解放军总医院胸外科,北京100853 [2]解放军总医院核医学科,北京100853

出　　处：《功能与分子医学影像学（电子版）》2014年第2期11-15,共5页Functional and Molecular Medical Imaging(Electronic Edition)

基　　金：北京市自然科学基金(7122162)

摘　　要：目的开发含-DEVD-核心的正电子核素18F标记的Caspase3多肽活性显像药物,用于肿瘤化疗后细胞凋亡的显像研究。方法应用修改后的国产多功能模块采用"点击化学"合成18F-Pen-peptide,并经HPLC和质谱证实。荷A549肺癌小鼠经卡铂化疗(24 h、48 h、72 h)后,尾静脉注射18F-Penpeptide,注射60 min后处死检测生物学分布,定量测量肿瘤化疗后的细胞凋亡率;每组荷瘤小鼠各取2只用Micro PET/CT显像。结果 "点击化学"合成18F-Pen-peptide的效率为(21.0±4.5)﹪(n=6),放化纯>99﹪,质谱证实标记物分子量为1153.6。荷A549肿瘤卡铂化疗后24 h、48 h、72 h,肿瘤对放射性摄取率分别为(0.33±0.02)﹪ID/g、(0.26±0.01)﹪ID/g、(0.21±0.01)﹪ID/g;明显高于对照组肿瘤摄取的(0.08±0.01)﹪ID/g(P<0.01);肿瘤对放射性的摄取量与肿瘤的凋亡相一致(P<0.01);Micro PET显像表明,对照组肿瘤基本不摄取放射性,肿瘤/肌肉的摄取比为(1.32±0.01),而经卡铂化疗后的肿瘤明显摄取放射性,肿瘤/肌肉的摄取比为(3.46±0.02),两者比较差异有统计学意义(P<0.01)。结论 18F-Pen-peptide是一个与Caspase3活性相关的显像剂,在监测肿瘤细胞凋亡方面有一定的临床潜在价值。Objective A caspase3-activatable probe, which contained Asp-Glu-Val-Asp（DEVD）, was synthesized with ^18F by ＂Click Chemistry＂ and was used for the imaging of apoptosis in vivo. Methods 18F-Penpeptide was synthesized by a modified home-made synthesized module using ＂click chemistry＂ and confirmed by HPLC and LC/MS/MS. Mice with A549 lung adenocarcinoma were treated by carboplatin and then injected with 18F-Pen-peptide 24, 48 and 72 hours after the treatment respectively. 60 minutes later the mice were sacrificed and the tumor apoptosis was measured. The Micro PET was performed with on two mice in each group. Results The yield of 18F-Pen-peptide was（21.0 ± 4.5） ﹪（n = 6）. The radiochemistry purity was over 99 ﹪. The formula weigh was 1153.6 by LC/MS/MS. The A549 tumor uptake was（0.33 ± 0.02）﹪ID/g,（0.26 ± 0.01） ID/g,（0.21 ± 0.01） ID/g at 24 h, 48 h and 72 h after chemotherapy respectively, significantly higher than the control group（0.08 ± 0.01） ﹪ ID/g（P 0.01）. The cell apoptosis rates agreed with radioactivity uptake of tumor. The Micro PET showed that there was no uptake in un-treated tumor with the T/NT of（1.32 ± 0.01）, and that there was obviously radioactivity accumulated in treated tumor with the T/NT of（3.46 ± 0.02）（P 0.01）. Conclusions ^18F-Pen-peptide is a radiotracer with great clinical potential for imaging of caspase-3 activation in tumor apoptosis.

关 键 词：肿瘤疗效评价 分子显像 凋亡 肿瘤 

分 类 号：R730.53[医药卫生—肿瘤]