[¹⁸F]Tetrafluoroborate ([¹⁸F]TFB) and its analogs for PET imaging of the sodium/iodide symporter

Sodium/iodide symporter (NIS)-mediated iodide uptake in thyroid follicular cells is the basis of clinical utilization of radioiodines. The cloning of the NIS gene enabled applications of NIS as a reporter gene in both preclinical and translational research. Non-invasive NIS imaging with radioactive iodides and iodide analogs has gained much interest in recent years for evaluation of thyroid cancer and NIS reporter expression. Although radioiodines and [^99mTc]pertechnetate ([^99mTc]TcO₄^-) have been utilized in positron emission tomography (PET) and single photon emission computed tomography (SPECT), they may suffer from limitations of availability, undesirable decay properties or imaging sensitivity (SPECT versus PET). Recently, [¹⁸F]tetrafluoroborate ([¹⁸F]TFB or [¹⁸F]BF₄^-) and other fluorine-18 labeled iodide analogs have emerged as a promising iodide analog for PET imaging. These fluorine-18 labeled probes have practical radiosyntheses and biochemical properties that allow them to closely mimic iodide transport by NIS in thyroid, as well as in other NIS-expressing tissues. Unlike radioiodides, they do not undergo organification in thyroid cells, which results in an advantage of relatively lower uptake in normal thyroid tissue. Initial clinical trials of [¹⁸F]TFB have been completed in healthy human subjects and thyroid cancer patients. The excellent imaging properties of [¹⁸F]TFB for evaluation of NIS-expressing tissues indicate its bright future in PET NIS imaging. This review focuses on the recent evolution of [¹⁸F]TFB and other iodide analogs and their potential value in research and clinical practice.