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

• Published in: EJNMMI research Vol. 7; no. 1; pp. 1 - 9
• Main Authors: Jiang, Huailei, Schmit, Nicholas R., Koenen, Alex R., Bansal, Aditya, Pandey, Mukesh K., Glynn, Robert B., Kemp, Bradley J., Delaney, Kera L., Dispenzieri, Angela, Bakkum-Gamez, Jamie N., Peng, Kah-Whye, Russell, Stephen J., Gunderson, Tina M., Lowe, Val J., DeGrado, Timothy R.
• Format: Journal Article
• Language: English
• Published: Berlin/Heidelberg Springer Berlin Heidelberg 27.10.2017; Springer Nature B.V; SpringerOpen
• Subjects: 18F-fluorine; Background radiation; Biodistribution; Biomarkers; Bladder; Blood; Cancer; Cardiac Imaging; Computed tomography; Dosimeters; Dosimetry; High performance liquid chromatography; Human subjects; Imaging; Laboratories; Medicine; Medicine & Public Health; Metabolism; Metabolites; Nuclear Medicine; Oncology; Original Research; Orthopedics; PET imaging; Pharmacokinetics; Pharmacology; Positron emission; Radioactivity; Radiology; Safety; Salivary glands; Sodium/iodide symporter; Stability analysis; Stomach; Tetrafluoroborate; Thyroid cancer; Tomography; Urine; Tetrafluoroborate; F-fluorine; Sodium/iodide symporter; Dosimetry; PET imaging; Biodistribution
• ISSN: 2191-219X; 2191-219X
• DOI: 10.1186/s13550-017-0337-5

Background 18 F-Tetrafluoroborate ( 18 F-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 18 F-TFB in healthy human subjects. Methods 18 F-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 18 F-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 18 F-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 18 F-radioactivity with the two rapid clearance phases over the first 20 min, followed by a slower clearance phase. HPLC analysis showed insignificant 18 F-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 18 F-TFB was prominent. Metabolic stability was evidenced by low accumulation of 18 F-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 18 F-TFB was safe and distributed in the human body similar to other iodide analogs. These data support further translational studies with 18 F-TFB as NIS gene reporter and imaging biomarker for thyroid cancer and other disease processes that import iodide.