^18F-FLT与^18F-FDG评估化疗早期反应的细胞学研究

目的:比较18F-FLT与18F-FDG在评估肺腺癌化疗早期反应的敏感性和准确性.材料和方法:选择氟尿嘧啶、阿霉素、顺铂3 种化疗药物,分别与肺腺癌A549细胞共同孵育1、4、24和72 h,测定细胞摄取18F-FLT和18F-FDG的变化,与药敏试验MTT法测定的存活细胞数目和细胞抑制率比较,判断两种示踪剂评估化疗反应的敏感性和准确性. 结果:(1)18F-FDG摄取变化:化疗后1h, 除5-FU组18F-FDG摄取明显增高(120±8%,P<0.01)外,顺铂和阿霉素组基本不变.4h、24h,三组变化也无明显变化.72h,三组均明显降低(35±3%,50±2%,55±4%,P<0.01).(2)18F-FLT摄取变化:3种细胞抑制剂均引起18F-FLT摄取明显变化,但变化趋势不同.5-FU对18F-FLT摄取的影响是双相的,治疗后1 h、4h,摄取增加(145±12%,P<0.01 ;150±14%,P<0.01);24h和72h明显减少(43±4%,60±4%P<0.01).阿霉素和顺铂引起18F-FLT摄取变化趋势基本相同,治疗后1h就观察到18F-FLT摄取迅速减少(70±6%,85±4%,P<0.01),24h摄取几乎全部被抑制(26±2%,15±4%,P<0.01).72h摄取较对照组仍降低(35±1%,30±2%,P<0.01).结论:18F-FLT能否反映化疗反应取决于药物的作用机制,5-FU 治疗后激活了肿瘤 DNA 补救合成途径而使早期摄取增高,相反,顺铂和阿霉素则引起摄取减低. 18F-FDG 摄取变化不明显.

An Experimental Study on the Early Changes in 18F-FLT and 18F-FDG Uptake of Tumor Cells after Chemotherapy

Purpose:The efficacy of evaluation of changes of tumoral uptake of 3'-deoxy-3'-[~(18)F] fluorothymidine (FLT) was comparatively analyzed with that of ~(18)F-FDG at early stage after anticancer chemotherapy.Materials and Methods:Cells derived from human lung adenocarcinoma were incubated with cisplatin (CDDP),5-fluorouracil(5-FU),doxorubicin (Dox),for 1,4,24 and 72h.The doses(CD-DP: 67 μM; 5-FU 1,540 μM;MTX: 440 μM;) were determined corresponding to a estimated 10% - 95% proliferation inhibition.The cells were allowed to recover before FLT or FDG being added into the culture media for 60 min.Cell counts,viability,estimated by MTT method,were used to evaluate the cytotoxic effects of chemotherapy.Results: FLT uptake was increased significantly at 1 and 4 h after treatment with 5-FU( 145 ± 12%,150 ± 14%,P <0.01).decreased at 24 h and 72 h.In contrast,FLT accumulation was significantly reduced at cytostatic concentrations of CDDP at different time.The uptake of FDG did not change significantly at early time points after treatment,but decreased at 72 h.Conclusion: The tumor cell uptake of FLT revealed specific changes depending on the auti-cancer drug used at much earlier time than FDG after chemotherpay.