^(18)F-FLT摄取与肺癌细胞增殖的相关性  

Correlation of 3′-Deoxy-3′-^(18)F-Fluorothymidine Uptake to Cell Proliferation in Lung Carcinoma Xenografts

作　　者：柳曦[1] 周乃康[1] 张锦明[2] 梁朝阳[1] 郑昕[1] 

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：《癌症》2006年第12期1512-1516,共5页Chinese Journal of Cancer

摘　　要：背景与目的:近年来,3′-脱氧-3′-18F-氟代胸苷(3′-deoxy-3′-18F-fluoro-thymidine,18F-FLT)被认为是反映肿瘤细胞增殖的新的PET(positronemissiontomography)示踪剂。本实验旨在研究18F-FLT在荷肺癌小鼠的生物分布和PET显像,并探讨18F-FLT摄取与肺癌细胞增殖的相关性。方法:48只荷肺腺癌T739小鼠根据示踪剂不同被随机分为18F-FLT组和18F-氟代脱氧葡萄糖(2-18F-fluoro-2-deoxy-D-glucose,18F-FDG)组两组,各组再分为3组(每组8只):(A)对照组;(B)治疗后1天组;(C)治疗后2天组。治疗组采用顺铂进行治疗。所有小鼠经尾静脉注入18F-FLT或18F-FDG,注药后60min用井型探测仪测量小鼠18F-FLT和18F-FDG的生物分布,并行PET显像。肿瘤增殖判定采用免疫组化测定增殖细胞核抗原(proliferatingcellnuclearantigen,PCNA)。结果:在两组对照组中,两种示踪剂的肿瘤PET显像均很清晰。生物分布研究显示肿瘤均有大量放射性摄取,肿瘤在血液、肌肉和肺的T/NT比值均>2.0。18F-FLT组顺铂治疗后肿瘤PCNA阳性率明显减低[A组(90.3±3.9)%ID/g,B组(65.5±9.2)%ID/g,C组(47.7±7.2)%ID/g],18F-FDG组同样明显减低[A组(91.2±3.5)%ID/g,B组(67.8±8.2)%ID/g,C组(45.9±9.1)%ID/g]。治疗后肿瘤18F-FLT摄取快速降低[A组(1.25±0.19)%ID/g,B组(0.82±0.19)%ID/g,C组(0.37±0.17)%ID/g],较18F-FDG摄取变化明显[A组(8.83±1.73)%ID/g,B组(7.88±1.78)%ID/g,C组(7.45±1.67)%ID/g]。PET显像证实B组和C组较A组肿瘤部位18F-FLT放射性浓聚减低。PCNA阳性率与肿瘤18F-FLT摄取呈显著相关性(r=0.930,P<0.001),而与18F-FDG摄取无相关性(r=-0.136,P=0.538)。结论:肺恶性肿瘤组织中18F-FLT摄取高于正常组织,通过PET能清楚显示肺恶性肿瘤;肿瘤18F-FLT摄取与PCNA阳性率的相关性较18F-FDG显著。18F-FLT是一种可反映肺癌细胞增殖的PET示踪剂。BACKGROUND ＆ OBJECTIVE： 3＇-Deoxy-3＇-^18F-fluorothymidine （^18F-FLT） has been described recently as a new positron emission tomography （PET） tracer for imaging tumor cell proliferation. This study was to investigate the biodistribution and PET imaging of ^18F-FLT in a murine model of lung cancer, and to explore the correlation of ^18F-FLT uptake to cell proliferation of lung cancer. METHODS： A total of 48 T739 mice bearing lung adenocarcinoma were randomized into ^18F-FLT group and 2-^18F-fiuoro-2-deoxy-D- glucose （^18F-FDG） group according to the radioactive tracers. Each group was also devided into 3 subgroups. （A） untreated controls, （B） 1 day after treatment of cisplatin, （C） 2 days after treatment of cisplatin. Each subgroup contained 8 mice. All mice were injected with^18F-FLT or ^18F-FDG through the tail veins. The biodistribution of ^18F-FLT and ^18F-FDG in tumor tissue was measured with well-gamma detector 60 min after injection; the PET imaging of mice was performed. Tumor cell proliferation was determined by immunohistochemical examination of proliferating cell nuclear antigen （PCNA）. RESULTS. In both subgroups A, the PET images of the tracers in tumor were clear. Considerable radioactive uptake of tumor was observed; the T/NT ratios of tumor/blood, tumor/muscle and tumor/lung were all above 2.0. The positive rate of PCNA was reduced significantly in ^18F-FLT group after treatment of cisplatin [（90.3±3.9）% （A） vs. （65.5±9.2）% （B） and （47.4±7.2）% （C）, P〈 0.01], and in ^18F-FDG group [（91.2±3.5）% （A） vs. （67.8±8.2）% （B） and （45.9±9.1）% （C）, P〈0.01]. Tumor uptake of ^18F-FLT was decreased rapidly after treatment [（1.25±0.19） %ID/g （A） vs. （0.82±0.19） %ID/g （B） and （0.37±0.17） %ID/g（C）, P〈0.01]; tumor uptake of 18F-FDG was decreased slightly after treatment [（8.83±1.73）%ID/g （A） vs. （7.88±1.78）% ID/g （B） and （7.45±1.67）%ID/g（C）, P〉0.05]. The PET imaging co

关 键 词：^18F-FLT ^18F-FDG PET显像 生物分布 肺肿瘤 细胞增殖 PCNA 同种移植物 动物模型 小鼠 

分 类 号：R734.2[医药卫生—肿瘤]