PURPOSE:The aim was to evaluate the incremental diagnostic rate of F-18 fluoro-fluorodeoxygulose positron emission tomography/computed tomography (F-18 FDG-PET/CT) in patients with negative I-131 whole body scans and high Tg levels. The secondary end points were correlations between F-18 FDG-PET/CT positive results and Tg levels and comparison between F-18 FDG-PET/CT accuracy in patients “on-therapy” with suppressed thyroid stimulating hormone (TSH) and those with high TSH levels. METHODS:We studied 52 patients who had undergone total thyroidectomy and remnant ablation; they had high Tg levels (average = 156 ng/mL; SD ± 274) after 3 weeks of levothyroxine withdrawal and negative I-131 total body scans after therapeutic doses. RESULTS:We noted a statistically significant positive correlation between F-18 FDG-PET/CT positive results and Tg levels, irrespective of levothyroxine therapy regimen. Tg levels between F-18 FDG-PET/CT positive/negative groups were significantly different and we did not note any statistically significant correlation between F-18 FDG-PET/CT results and TSH levels, tumor size, and combination of Tg/TSH levels. CONCLUSIONS:Our results indicate that F-18 FDG-PET/CT is a useful diagnostic tool in patients with differentiated thyroid carcinoma and with negative I-131 total body scans and high Tg levels. The levothyroxine therapy regimen does not influence F-18 FDG-PET/CT results and the rate of F-18 FDG-PET/CT positive results appears to correlate with the Tg levels. The highest accuracy is reached when the study is performed for patients with Tg levels higher than 21 ng/mL.