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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72h,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1h、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。
OBJECTIVE: To compare the sensitivity and accuracy of 18F-FLT and 18F-FDG in assessing the early response to chemotherapy of lung adenocarcinoma. MATERIALS AND METHODS: Three chemotherapeutic agents, fluorouracil, doxorubicin, and cisplatin, were selected and incubated with A549 cells respectively for 1, 4, 24 and 72 h. The uptake of 18F-FLT and 18F-FDG were measured. The sensitivity and accuracy of two tracer to evaluate the response of chemosensitivity were compared between the number of surviving cells and the cell inhibition rate determined by MTT assay. Results: (1) The changes of 18F-FDG uptake: At 1 hour after chemotherapy, the uptake of 18F-FDG in 5-FU group was not significantly changed except that of 18F-FDG uptake (120 ± 8%, P <0.01). 4h, 24h, no significant changes in the three groups. 72h, the three groups were significantly reduced (35 ± 3%, 50 ± 2%, 55 ± 4%, P <0.01). (2) 18F-FLT uptake changes: 3 kinds of cytostatic agents caused significant changes in 18F-FLT uptake, but the trend of change. The effect of 5-FU on the uptake of 18F-FLT was biphasic. After 1h and 4h treatment, the uptake of 5-FU increased significantly (145 ± 12%, P <0.01; 150 ± 14%, P <0.01) ± 4%, 60 ± 4% P <0.01). Uptake of 18F-FLT by doxorubicin and cisplatin tended to be almost the same, with a rapid decrease of 18F-FLT uptake (70 ± 6%, 85 ± 4%; P <0.01) (26 ± 2%, 15 ± 4%, P <0.01). 72h uptake than the control group is still reduced (35 ± 1%, 30 ± 2%, P <0.01). CONCLUSION: Whether 18F-FLT can reflect the mechanism of chemotherapy depends on the mechanism of action of drugs. After 5-FU treatment, the DNA synthesis pathway of tumor DNA is activated and the early intake is increased. On the contrary, cisplatin and doxorubicin cause the decrease of uptake. 18F-FDG uptake was not obvious.