Abstract
682
Objectives: 18F-TFB has been identified as a promising iodide analog for imaging of thyroid cancer and monitoring of NIS expression as a reporter probe in viral therapy applications. In this study, a cGMP-compliant automated synthesis of 18F-TFB was developed and initial PET imaging studies to obtain biodistribution data in healthy human subjects.
Methods: 18F-TFB was synthesized with 18F-fluoride and BF3 solution on QMA cartridge. Dynamic PET/CT imaging over 4 h was performed after intravenous administration of 18F-TFB (333-407 MBq) in overnight-fasted 4 female and 4 male healthy subjects (35±10 year old). Initial scanning over the heart allowed definition of the blood clearance kinetics, while whole body scans at 2 and 3.5 h provided data for biodistribution. 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 determine the safety of 18F-TFB administration.
Results: 18F-TFB was synthesized in decay-corrected radiochemical yield of 32±2% and >98% radiochemical purity (RCP). Specific radioactivity of 2.2±0.9 GBq/µmol was achieved from starting 18F-fluoride radioactivity of 20-31 GBq. In vitro RCP remained >96% up to 8 h. 18F-TFB administration was well tolerated with no significant findings on vital signs or clinical laboratory assays. Left-ventricular blood pool time-activity curves showed a multi-phasic blood clearance of radioactivity with the two rapid clearance phases over the first 30-45 m, 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). At 2 h p.i., high uptakes (SUVs) were seen in thyroid (53±22), stomach (53±24), salivary glands (parotid gland: 16±11), and kidney (6.3±1.8). Urinary clearance of 18F-TFB was prominent. Minor changes were seen in 18F-TFB biodistribution from 2-4 h p.i. A low level of metabolic defluorination was evidenced by low accumulation of 18F-radioactivity in bone (SUV = 1.3±0.7 at 3.5 h).
Conclusion: An automated, cGMP synthesis method of high specific radioactivity 18F-TFB was developed. Initial studies in healthy human subjects showed the radiotracer to be safe, metabolically stable, and distribute in the human body similar to other iodide analogs with prominent physiologic distribution to thyroid, stomach, salivary glands and bladder. Research Support: This work was supported by NIH (CA196975).