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Early Detection of Chemoradioresponse in Esophageal Carcinoma by 3'-Deoxy-3'-³H-Fluorothymidine Using Preclinical Tumor Models

Authors' Affiliations: Departments of ¹ Radiation Oncology, ² Experimental Diagnostic Imaging, ³ Radiation Physics, ⁴ Imaging Physics, and ⁵ GI Medical Oncology, The University of Texas M.D. Anderson Cancer Center, Houston, Texas

Requests for reprints: K.S. Clifford Chao, Department of Radiation Oncology, The University of Texas M.D. Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, TX 77030. Phone: 713-563-2300; Fax: 713-563-2368; E-mail: cchao{at}mdanderson.org.

Purpose: Early identification of esophageal cancer patients who are responding or resistant to combined chemoradiotherapy may lead to individualized therapeutic approaches and improved clinical outcomes. We assessed the ability of 3'-deoxy-3'-¹⁸F-fluorothymidine positron emission tomography (FLT-PET) to detect early changes in tumor proliferation after chemoradiotherapy in experimental models of esophageal carcinoma.

Experimental Design: The in vitro and ex vivo tumor uptake of [³H]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 [¹⁸F]FLT micro-PET imaging. Imaging-histologic correlation was determined by comparing spatial Ki-67 and [¹⁸F]FLT distribution in autoradiographs. Comparison with fluorodeoxyglucose (FDG) was done in all experiments.

Results: In vitro [³H]FLT and [³H]Thd uptake rapidly decreased in SEG-1 cells 24 hours after docetaxel with a maximal reduction of over 5-fold (P = 0.005). The [³H]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 [³H]FDG uptake was gradual and less pronounced. Tumor uptake of [³H]FLT was more closely correlated with Ki-67 expression (r = 0.89, P < 0.001) than was [³H]FDG (r = 0.39, P = 0.08). Micro-PET images depicted similar trends in reduction of [¹⁸F]FLT and [¹⁸F]FDG tumor uptake. Autoradiographs displayed spatial correlations between [¹⁸F]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.

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