2.1.2. [18F]Tetrafluoroborate ([18F]TFB)

Detecting local recurrence and metastases of DTC in radioiodine imaging is particularly important for the arrangement of local treatments, e.g., surgery or radiotherapy [5]. Whereas negative radioiodine imaging with increased serum thyroglobulin is a barrier for finding malignant lesions, the so-called "Thyroglobulin Elevated and Negative Iodine

Scintigraphy" (TENIS) needs radically diverse diagnostic and therapeutic methods [26]. TENIS could be caused by poor NIS expression, iodide organification defect, or radioiodine stunning [41,42]. A failure to find NIS-expressing DTC lesions might delay the diagnosis and also the timely onset of the treatment [43]. Despite [18F]FDG-PET/CT could be applied for finding TENIS metastases, but its uptake might be partially caused by tumor-infiltrating immune cells [44]. Recently, [18F]TFB, [18F]Fluorosulfate ([18F]FS), and [ 18F]hexafluorophosphate ([18F]HFP) have been discovered for imaging DTCs [45–48].

[ 18F]TFB is an analog to radioiodine, having similar NIS affinities, same charge, and similar ionic radius to iodide. Therefore, [18F]TFB can be transported by NIS [46,49] differed from radioiodine, [18F]TFB can be readily synthesized at medical cyclotrons, and it provides a satisfactory half-life, dosing, biodistribution, and PET imaging quality [46,47] (Figure 3). [18F]TFB-PET can exclusively reveal NIS expression in tumor cells, therefore reclassifying TENIS metastases into partial or complete dedifferentiation, and helping metastasis localization and prognosis evaluation [47]. [18F]FS and [18F]HFP are two other newly discovered NIS-targeting tracers having favorable targeting efficiency, image contrasts, and biodistribution features [45,48]. Although it has been reported that FS and HFP had higher NIS affinity than TFB [45], it remains unclear if [18F]HFP and [18F]FS are superior to [18F]TFB. The clinical evaluation of the [18F]HFP and [18F]FS are still needed.

**Figure 3.** Evaluation of thyroid cancer via [18F]TFB-PET/CT and [124I]NaI-PET/CT. (**A**) Biodistribution of [18F]TFB at various time points on PET images. [18F]TFB accumulated rapidly in the thyroid and other normal tissues like the salivary gland and stomach within 10–30 min. Reproduced with permission from [50], copyright 2017 Society of Nuclear Medicine and Molecular Imaging. (**B**,**C**) A comparison between [124I]NaI-PET/CT and [18F]TFB-PET/CT in a 26-year-old patient post-thyroidectomy. (**B**) [124I]NaI-PET/CT was unremarkable for PTC. (**C**) In contrast, [18F]TFB-PET/CT revealed two foci in the left lateral cervical region. Reproduced with permission from [51], copyright 2018 Wolters Kluwer Health.
