Introduction Efficient therapy of recurrent differentiated thyroid cancer (DTC) is dependent on precise molecular imaging techniques targeting the human sodium iodide symporter (hNIS), which is a marker both of thyroid and DTC cells. Various iodine isotopes have been utilized for detecting DTC; however, these come with unfavorable radiation exposure and image quality ([ 131 I]iodine) or limited availability ([ 124 I]iodine). In contrast, [ 18 F]tetrafluoroborate (TFB) is a novel radiolabeled PET substrate of hNIS, results in PET images with high-quality and low radiation doses, and should therefore be suited for imaging of DTC. The aim of the present study was to compare the diagnostic performance of [ 18 F]TFB-PET to the clinical reference standard [ 131 I]iodine scintigraphy in patients with recurrent DTC. Methods Twenty-five patients with recurrent DTC were included in this retrospective analysis. All patients underwent [ 18 F]TFB-PET combined with either CT or MRI due to newly discovered elevated TG levels, antiTG levels, sonographically suspicious cervical lymph nodes, or combinations of these findings. Correlative [ 131 I]iodine whole-body scintigraphy (dxWBS) including SPECT-CT was present for all patients; correlative [ 18 F]FDG-PET-CT was present for 21 patients. Histological verification of [ 18 F]TFB positive findings was available in 4 patients. Results [ 18 F]TFB-PET detected local recurrence or metastases of DTC in significantly more patients than conventional [ 131 I]iodine dxWBS and SPECT-CT (13/25 = 52% vs. 3/25 = 12%, p = 0.002). The diagnosis of 6 patients with cervical lymph node metastases that showed mildly increased FDG metabolism but negative [ 131 I]iodine scintigraphy was changed: [ 18 F]TFB-PET revealed hNIS expression in the metastases, which were therefore reclassified as only partly de-differentiated (histological confirmation present in two patients). Highest sensitivity for detecting recurrent DTC had the combination of [ 18 F]TFB-PET-CT/ MRI with [ 18 F]FDG-PET-CT (64%). Conclusion In the present cohort, [ 18 F]TFB-PET shows higher sensitivity and accuracy than [ 131 I]iodine WBS and SPECT-CT in detecting recurrent DTC. The combination of [ 18 F]TFB-PET with [ 18 F]FDG-PET-CT seems a reasonable strategy to characterize DTC tumor manifestations with respect to their differentiation and thereby also individually plan and monitor treatment. Future prospective studies evaluating the potential of [ 18 F]TFB-PET in recurrent DTC are warranted.

Purpose Given the large number of patients with thyroid nodules, improvement of the specificity of current ultrasound-based thyroid nodule classification systems (ATA, EU-TIRADS, and ACR-TIRADS) is warranted to reduce the number of diagnostic thyroidectomies. Thyroid scintigraphy has been shown to demonstrate hyperfunctional nodules, associated with a low malignancy risk, in euthyroid patients. However, it is not known if thyroid scintigraphy could improve specificity of current classification systems. The aim of this study, therefore, was to determine the frequency of hyperfunctional nodules among those nodules in need of fine needle aspiration cytology (FNA) according to current classification systems and to test if nodule functional status is associated with sonographic features. Methods Five hundred sixty-six euthyroid patients (TSH 0.55-4.20 μU/ml) presenting for thyroid nodule workup including thyroid sonography and scintigraphy at our department between 09/2013 and 02/2018 were included in this retrospective study. All nodules > 10 mm were classified according to ATA, EU-TIRADS, and ACR-TIRADS and correlated to their functional status as assessed by 99m Tc-pertechnetate scintigraphy. Results Ultrasound detected 1029 thyroid nodules ≥ 10 mm, including 545 nodules ≥ 15 mm. Prevalence of hyperfunctional nodules among those with recommendation for FNA according to ATA 2015, EU-TIRADS, and ACR-TIRADS was 6.4%, 6.9%, and 6.5% for nodules ≥ 10 mm and 7.2%, 7.6%, and 7.5% only considering nodules ≥ 15 mm. No sonographic feature was correlated to hyperfunctionality of nodules. Conclusion In euthyroid patients, thyroid scintigraphy demonstrates hyperfunctionality, which cannot be predicted by ultrasound, in up to 6.9% of nodules in need of FNA according to ultrasound-based classifications. Given the known low risk of malignancy in hyperfunctional nodules, thyroid scintigraphy can lower the frequency of fine needle aspirations and-potentially-the frequency of diagnostic hemithyroidectomies in euthyroid patients.

A complete omission of DxWBS in the post-RRA surveillance of DTC is justified once DxWBS is negative and sTg is below the functional sensitivity (with no evidence of thyroglobulin antibodies), as patients showing this combination of test results (especially 12 months after RRA) show an at worst marginal risk of recurrence. In all other cases DxWBS may still be justified.