Safety, pharmacokinetics, metabolism and radiation dosimetry of ¹⁸F-tetrafluoroborate (¹⁸F-TFB) in healthy human subjects

Background: ¹⁸F-Tetrafluoroborate (¹⁸F-TFB) is a promising iodide analog for PET imaging of thyroid cancer and sodium/iodide symporter (NIS) reporter activity in viral therapy applications. The aim of this study was to evaluate the safety, pharmacokinetics, biodistribution, and radiation dosimetry of high-specific activity ¹⁸F-TFB in healthy human subjects. Methods: ¹⁸F-TFB was synthesized with specific activity of 3.2 ± 1.3 GBq/μmol (at the end of synthesis). Dynamic and whole-body static PET/CT scans over 4 h were performed after intravenous administration of ¹⁸F-TFB (333–407 MBq) in four female and four male healthy volunteers (35 ± 11 years old). Samples of venous blood and urine were collected over the imaging period and analyzed by ion-chromatography HPLC to determine tracer stability. Vital signs and clinical laboratory safety assays were measured to evaluate safety. Results: ¹⁸F-TFB administration was well tolerated with no significant findings on vital signs and no clinically meaningful changes in clinical laboratory assays. Left-ventricular blood pool time-activity curves showed a multi-phasic blood clearance of ¹⁸F-radioactivity with the two rapid clearance phases over the first 20 min, followed by a slower clearance phase. HPLC analysis showed insignificant ¹⁸F-labeled metabolites in the blood and urine over the length of the study (4 h). High uptakes were seen in the thyroid, stomach, salivary glands, and bladder. Urinary clearance of ¹⁸F-TFB was prominent. Metabolic stability was evidenced by low accumulation of ¹⁸F-radioactivity in the bone. Effective doses were 0.036 mSv/MBq in males and 0.064 mSv/MBq in females (p = 0.08, not significant). Conclusions: This initial study in healthy human subjects showed ¹⁸F-TFB was safe and distributed in the human body similar to other iodide analogs. These data support further translational studies with ¹⁸F-TFB as NIS gene reporter and imaging biomarker for thyroid cancer and other disease processes that import iodide.