Early detection of chemoradioresponse in esophageal carcinoma by 3′-deoxy-3′-3H-fluorothymidine using preclinical tumor models
Early detection of chemoradioresponse in esophageal carcinoma by 3′-deoxy-3′-3H-fluorothymidine using preclinical tumor models
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DOI：
10.1158/1078-0432.ccr-05-2720
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发表时间：
2006-08-01
影响因子：
11.5
通讯作者：
Chao, K. S. Clifford
中科院分区：
文献类型：
--
作者：
Apisarnthanarax, Smith;Alauddin, Mian M.;Chao, K. S. Clifford
目的：早期识别对联合放化疗有反应或耐药的食管癌患者可能会导致个体化治疗方法并改善临床结果。我们评估了 3'-脱氧-3'-F-18-氟胸苷正电子发射断层扫描 (FLT-PET) 在食管癌实验模型中检测化疗放疗后肿瘤增殖早期变化的能力。实验设计：在多西他赛加照射后的不同早期时间点研究了 SEG-1 人食管腺癌细胞对 [H-3] FLT 的体外和离体肿瘤摄取，并用常规方法进行了验证细胞增殖评估 [胸苷 (Thd) 和 Ki-67] 和 [F-18] FLT 微型 PET 成像。通过比较放射自显影照片中的空间 Ki-67 和 [F-18] FLT 分布来确定成像-组织学相关性。所有实验均与氟脱氧葡萄糖（FDG）进行比较。结果：多西他赛24小时后，SEG-1细胞的体外[H-3]FLT和[H-3]Thd摄取迅速下降，最大减少超过5倍（P = 0.005）。尽管肿瘤大小没有变化，但放化疗后 2 天，异种移植物中的 [H-3] FLT 肿瘤与肌肉摄取比与基线相比下降了 75% (P < 0.005)。相比之下，[H-3] FDG 吸收的下降是逐渐的且不太明显。 [H-3] FLT 的肿瘤摄取与 Ki-67 表达的相关性比 [H-3] FDG (r = 0.39, P = 0.08) 更密切 (r = 0.89, P < 0.001)。微型 PET 图像描绘了 [F-18] FLT 和 [F-18] FDG 肿瘤摄取减少的相似趋势。在初步研究中，放射自显影照片显示了 [F-18] FLT 摄取与组织学 Ki-67 分布之间的空间相关性。结论：FLT-PET 适合且比 FDG-PET 更特异，可用于描述放化疗后肿瘤大小变化之前肿瘤增殖的早期减少。
Purpose: Early identification of esophageal cancer patients who are responding or resistant to combined chemo radiotherapy may lead to individualized therapeutic approaches and improved clinical outcomes. We assessed the ability of 3'-deoxy-3'-F-18-fluorothymidine positron emission tomography (FLT-PET) to detect early changes in tumor proliferation after chemo radiotherapy in experimental models of esophageal carcinoma.Experimental Design: The in vitro and ex vivo tumor uptake of [H-3] FLT in SEG-1 human esophageal adenocarcinoma cells were studied at various early time points after docetaxel plus irradiation and validated with conventional assessments of cellular proliferation [thymidine (Thd) and Ki-67] and [F-18] FLT micro-PET imaging. Imaging-histologic correlation was determined by comparing spatial Ki-67 and [F-18] FLT distribution in autoradiographs. Comparison with fluorodeoxyglucose (FDG) was done in all experiments.Results: In vitro [H-3]FLT and [H-3]Thd uptake rapidly decreased in SEG-1 cells 24 hours after docetaxel with a maximal reduction of over 5-fold (P = 0.005). The [H-3] FLT tumor-to-muscle uptake ratio in xenografts declined by 75% compared with baseline (P < 0.005) by 2 days after chemoradiotherapy, despite the lack of change in tumor size. In contrast, the decline of [H-3] FDG uptake was gradual and less pronounced. Tumor uptake of [H-3] FLT was more closely correlated with Ki-67 expression (r = 0.89, P < 0.001) than was [H-3] FDG (r = 0.39, P = 0.08). Micro-PET images depicted similar trends in reduction of [F-18] FLT and [F-18] FDG tumor uptake. Autoradiographs displayed spatial correlations between [F-18] FLT uptake and histologic Ki-67 distribution in preliminary studies.Conclusions: FLT-PET is suitable and more specific than FDG-PET for depicting early reductions in tumor proliferation that precede tumor size changes after chemoradiotherapy.