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SUMMARY We used pathological examination as golden standard to determine whether 3-deoxy-3-18F-fluorothymidine positron emission tomography/computed tomography (FLT PET/CT) can detect regional lymph node metastasis in untreated thoracic esophageal squamous cell carcinoma and additionally performed 18F-fluorodeoxyglucose (FDG) PET/CT for direct comparison with that of FLT. Twenty-two patients with thoracic esophageal squamous cell carcinoma underwent dual-tracer PET/CT examinations before surgery. The results of reviewing CT images and side-by-side FDG PET and FLT PET images for the diagnosis of locoregional lymph node metastasis were compared prospectively in relation to pathologic findings. All patients underwent esophagectomy and lymphadenectomy. Pathologic examination confirmed nodes positive for metastasis in 16 patients and 47 of 424 excised nodes. The uptake of FDG (median SUVmax, 5.4; range, 2.4-10.6) in locoregional lymph nodes metastases was significantly higher than that of FLT (median SUVmax, 2.8; range, 1.3-4.6). There were 14 false-positive nodes in FDG PET/CT and only 3 in FLT PET/CT; 8 false-negative nodes in FDG PET/CT, while there were 12 false negative nodes in FLT PET/CT. The sensitivity, specificity, accuracy, positive predictive value, and negative predictive value of FLT PET/CT were 74.47%, 99.20%, 96.46%, 92.11%, and 96.89%, respectively, whereas those of FDG PET/CT were 82.98%, 96.29%, 94.81%, 82.98%, and 96.29%, respectively. P-values were 0.450, 0.014, 0.313, 0.050, and 0.555, respectively. FLT uptake in regional lymph nodes of esophageal carcinoma is significantly lower compared with FDG uptake. FLT PET/CT has fewer false-positive findings and higher specificity compared with FDG PET/CT. [ABSTRACT FROM AUTHOR]