Thyroglobulin doubling time offers a better threshold than thyroglobulin level for selecting optimal candidates to undergo localizing [${}^{18}$F]FDG PET/CT in non-iodine avid differentiated thyroid carcinoma

To investigate the potential role of serum thyroglobulin doubling time (TgDT) in predicting 2-deoxy-2-[${}^{18}$F]fluoro-d-glucose ([${}^{18}$F]FDG) PET/CT results in patients affected by differentiated thyroid carcinoma (DTC) who demonstrated a combination of positive Tg but a negative [${}^{131}$I] whole-body scan ([${}^{131}$I]-WBS). Inclusion criteria were (1) prior [${}^{131}$I] treatment for DTC, (2) negative subsequent [${}^{131}$I]-WBS, (3) no interfering anti-Tg antibodies, (4) three consecutive Tg measurements under the thyroid hormone replacement therapy to calculate TgDT before 2-[${}^{18}$F]FDG PET/CT, and (5) at least 6 months of clinical and/or imaging follow-up to ascertain the diagnosis. Receiver operating characteristic (ROC) curve and the area under the curve (AUC) were used to identify the optimal cutoff point for the last stimulated Tg and TgDT prior to [${}^{18}$F]FDG PET/CT. One hundred and thirteen patients were included. Seventy-four (65%) patients had positive [${}^{18}$F]FDG PET/CT for DTC recurrence, while the remaining 39 (35%) negative. Sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of [${}^{18}$F]FDG PET/CT were 92%, 94%, 97%, 87%, and 93%. Patients with positive [${}^{18}$F]FDG PET/CT had higher Tg and TgDT than those with negative PET/CT. ROC curve analysis revealed an optimal Tg cutoff of 19 ng/mL (sensitivity 78%, specificity 85%, AUC = 0.844) and TgDT of 2.5 years (sensitivity 93%, specificity 87%, AUC = 0.911). TgDT threshold of 2.5 years predicted significantly (p = 0.023) better than Tg level PET/CT results. The diagnostic performance of [${}^{18}$F]FDG PET/CT could be significantly improved when TgDT is less than or equal to 2.5 years, as compared with using the absolute Tg level.