Synthesis and In Vivo Evaluation of p-18F-Fluorohippurate as a New Radiopharmaceutical for Assessment of Renal Function by PET

The molecular structure of p-F-18-fluorohippurate (F-18-PFH) is similar to that of p-aminohippurate, a gold standard for the measurement of effective renal plasma flow. The objective of this study was to investigate F-18-PFH as a new PET renal agent. Methods: F-18-PFH was synthesized by reacting N-succinimidyl-4-F-18-fluorobenzoate (F-18-SFB) with glycine at 90 degrees C (pH 8) for 20 min. In vitro stability was determined by incubating F-18-PFH in fresh human plasma at 37 degrees C for 60 min. In vivo stability was determined by high-performance liquid chromatography analysis of urine collected from a normal rat at 40 min after injection of F-18-PFH. The plasma protein binding and erythrocyte uptake were determined using plasma collected from a normal rat at 5 min after injection of F-18-PFH. The plasma clearance of F-18-PFH was determined using a single-injection clearance method in normal and probenecid-treated rats. Biodistribution studies were conducted in normal rats at 10 min and 1 h after injection of F-18-PFH. Dynamic PET/CT studies were conducted in normal rats injected with F-18-PFH. Results: In normal rats, the plasma clearance of F-18-PFH was 4.11 +/- 1.09 mL/min/100 g, which reduced by approximately 50% (P = 0.03) to 2.01 +/- 0.08 mL/min/100 g in probenecid-treated rats. About 45.3% of F-18-PFH was found to associate with plasma proteins in vivo in normal rats. Biodistribution studies of F-18-PFH in normal rats showed 72.1 +/- 6.4 percentage injected dose and 88.6 +/- 6.2 percentage injected dose, respectively, in urine at 10 min and 1 h after injection. The uptake in other organs was negligible. High-performance liquid chromatography analysis of urine collected from a rat at 40 min after injection of F-18-PFH indicated that it was excreted intact, with no metabolic products. Dynamic PET revealed a rapid clearance of F-18-PFH through the renal-urinary pathway. The PET-derived renograms revealed a time to peak activity of 3.0 +/- 1.0 min. Conclusion: These combined results warrant further investigation of F-18-PFH as a radiopharmaceutical for the assessment of renal function by PET.