59 Diagnostic utility of molecular and imaging biomarkers 2 adenoma had an SUVmax ≥2 and all other benign lesions an SUVmax <2, in multiple other studies the SUVmax of benign and malignant indeterminate thyroid nodules overlapped. No threshold could accurately tell them apart [37, 59, 306, 308, 309, 311, 312]. Moreover, as SUVmax calculations strongly depend on image acquisition and reconstruction methods, type of PET-scanner and other variable methodology, reported absolute SUVmax thresholds are not simply valid for other institutions [59]. Standardized optimized [18F]FDG-PET protocols are required for inter-institution comparison of study results and advancement of PET research [313, 314]. [18F]FDG-PET in thyroid nodules with Hürthle cell cytology Multiple studies observed aberrant [18F]FDG-PET characteristics in indeterminate nodules with Hürthle cell cytology: both benign and malignant lesions are mostly [18F]FDG-positive. Twenty-nine Hürthle cell lesions were reported by Deandreis et al., consisting 52% of their study population and providing an explanation for their limited sensitivity [309]. Moreover, Hürthle cell adenoma generally demonstrated a significantly higher SUVmax than other benign lesions [37, 59, 303, 305, 309, 315]. The proportion of Hürthle cell cytology in individual studies is relatively small, but overall [18F]FDG-PET seems inadequate in these neoplasms. Availability, cost-effectiveness and limitations of [18F]FDG-PET PET systems are less widely available than conventional gamma cameras. Moreover, 18F used for 18F-FDG synthesis is produced in cyclotrons, and transport distances are limited due to the short half-life of this isotope (~110 min). In Europe, [18F]FDG-PET/CT is approximately 1.5-2 times more expensive than [99mTc]Tc-MIBI SPECT/CT. The radiation exposure of [18F]FDG-PET/CT is largely accounted for by the [18F]FDG dosage at approximately 19 μSv/MBq, i.e. about 3-4 mSv for a typical activity of 185 MBq administered to an average adult [316]. Insights regarding common practice total-body [18F]FDG-PET/CT imaging are changing [307, 309]. The CT radiation dose greatly varies, and can be less than 0.5 mSv for a low-dose CT of the neck region only. When scanning the thyroid region only, a longer imaging time can compensate for a reduction in [18F]FDG dose, which would lower the radiation burden as well as the costs. Such solutions may counter prevailing reservations regarding ionizing radiation exposure. Additionally, partial-body acquisition could limit the number of coincidental PET-positive findings. Much of the criticism on [18F]FDG-PET focuses on these potential incidental findings, which require additional diagnostics, are not always clinically relevant and may negatively impact potential cost-effectiveness [317, 318]. Malignant ipsi- or contralateral thyroid incidentalomas are reported while the nodule under investigation was histopathologically benign [307, 308]. PET-positive incidentalomas are histopathologically malignant in about 20% of patients [318]. Cost-effectiveness of [18F]FDG-PET/CT was modelled by Vriens et al. [53]. From a Dutch health care perspective, [18F]FDG-PET/CT driven treatment would decrease the rate of unbeneficial diagnostic hemithyroidectomies for benign thyroid nodules by 35% and reduce the costs per patient by €822 compared to the €8,804 expenses for conventional surgical treatment. Also, [18F]FDG-PET/ CT was favoured over the miRInform® and Afirma® GEC [53].
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