^(18)氟-氟代脱氧葡萄糖与^(18)氟-氟代胸腺嘧啶用于吉西他滨联合顺铂治疗非小细胞肺癌动物模型的早期疗效监测比较

Comparison of early response to combined chemotherapy gemcitabine-cisplatin in nonsmall cell lung cancer animal model between using ^(18)F-fluorodeoxyglucose and ^(18)F-fluorothymidine

非小细胞肺癌(NSCLC)约占肺癌的80%以上,吉西他滨联合顺铂已成为目前治疗NSCLC的一线化疗方案。本研究旨在探讨^(18)氟-氟代脱氧葡萄糖(^(18)F-FDG)和^(18)氟-氟代脱氧胸腺嘧啶(^(18)F-FLT)的小动物正电子(micro PET)显像早期监测吉西他滨联合顺铂治疗NSCLC疗效的价值。以荷Lewis肺癌的C57BL/6小鼠作为动物模型,实验组给予吉西他滨加顺铂联合化疗,对照组给予等量生理盐水处理。分别在治疗前和治疗后第3天进行^(18)F-FDG和^(18)F-FLT的micro PET显像,观察实验组及对照组动物肿瘤体积及^(18)F-FDG、^(18)F-FLT摄取的变化。显像结束后处死部分小鼠,取肿瘤组织进行苏木精-伊红(HE)染色及抗原Ki67免疫组化染色。与对照组相比,实验组的肿瘤生长明显受到抑制(P<0.05)。在实验组中,^(18)F-FLT的最大标准化摄取值(SUVmax)从治疗前的0.59±0.05下降至治疗后第3天的0.28±0.05,结果显示差异具有统计学意义(P<0.05),而^(18)F-FDG的SUVmax从治疗前的4.35±0.46下降至治疗后第3天的4.02±0.47,结果显示差异不具有统计学意义(P>0.05)。组织学结果显示,在采用吉西他滨加顺铂治疗后,肿瘤增殖指标抗原Ki67出现明显下降(P<0.05)。HE染色提示化疗后肿瘤组织中有较多坏死细胞及炎性细胞。本研究结果提示,^(18)F-FLT比^(18)F-FDG能够更早期监测吉西他滨联合顺铂治疗NSCLC的效果;此外,^(18)F-FLT受化疗后肿瘤组织中的炎症反应干扰更小。

Non-small cell lung cancer （NSCLC） accounts for more than 80% of lung cancer. Nowadays, gemcitabine and cisplatin in combination have been adopted as the first-line chemotherapy for patients with NSCLC. This study aimed to monitor early response to combined chemotherapy of gemcitabine plus cisplatin in a mouse model of NSCLC by using ^18F-fluorodeoxyglucose and ^18F-fluorothymidine small animal positron emission tomography （PET）. Lewis lung carcinoma-bearing C57BL/6 mice were treated with gemcitabine-cisplatin or saline. Small animal PET with ^18F-FDG and ^18F-FLT was performed before （baseline） and after treatment （on Day 3）, respectively. Imaging results were confirmed by histopathological studies （hematoxylin and eosin staining, Ki67 staining）. Compared to the results in the control group, gemcitabine-cisplatin in the treated group significantly inhibited tumor growth （P〈0.05）. In the treated group, the maximum standardized uptake value （SUVmax） of ^18F-FLT decreased significantly from 0.59±0.05 （baseline） to 0.28±0.05 （Day 3） （P〈0.05）. There was no significant difference between baseline （4.35±0.46） and that on Day 3 （4.02± 0.47） on ^18F-FDG SUVmax （P〉0.05）. The proliferation of tumor assessed by Ki67 staining decreased significantly after treatment of one dose ofgemicitabine-cisplatin （P〈0.05）. The staining of HE showed an increase in necrotic and inflammatory cells after the treatment. This study demonstrated that the uptake of ^18F-FLT reduced more rapidly and significantly than that of ^18F-FDG and was less disturbed by the increase of inflammatory cells after chemotherapy.