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The nucleoside analog 3′-deoxy-3′-18F-fluorothymidine (FLT) has been introduced for imaging cell proliferation with positron emission tomography (PET). We prospectively compared the diagnostic efficacy of FLT PET with that of 2-deoxy-2-18F-fluoro-D-glucose (FDG) PET for the preoperative nodal and distant metastatic staging of non-small cell lung cancer (NSCLC).A total of 34 patients with NSCLC underwent FLT PET and FDG PET. PET imaging was performed at 60 min after each radiotracer injection. The PET images were evaluated qualitatively for regions of focally increased metabolism. For visualized primary tumors, the maximum standardized uptake value (SUV) was calculated. Nodal stages were determined by using the American Joint Committee on Cancer staging system and surgical and histologic findings reference standards.For the depiction of primary tumor, sensitivity of FLT PET was 67%, compared with 94% for FDG PET (P = 0.005). Sensitivity, specificity, positive predictive value, negative predictive value, and accuracy for lymph node staging on a per-patient basis were 57, 93, 67, 89, and 85%, respectively, with FLT PET and 57, 78, 36, 91, and 74%, respectively, with FDG PET (P > 0.1 for all comparisons). Two of the three distant metastases were detected with FLT and FDG PET.In NSCLC, FLT PET showed better (although not statistically significant) specificity, positive predictive value and accuracy for N staging on a per-patient basis than FDG PET. However, FDG PET was found to have higher sensitivity for depiction of primary tumor than FLT PET.