title: Synthesis and in vivo evaluation of p-18F-Fluorohippurate as a new radiopharmaceutical for assessment of renal function by PET.
abstract: The molecular structure of p-18F-fluorohippurate (18F-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 18F-PFH as a new PET renal agent.
  
  
  METHODS
  18F-PFH was synthesized by reacting N-succinimidyl-4-18F-fluorobenzoate (18F-SFB) with glycine at 90°C (pH 8) for 20 min. In vitro stability was determined by incubating 18F-PFH in fresh human plasma at 37°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 18F-PFH. The plasma protein binding and erythrocyte uptake were determined using plasma collected from a normal rat at 5 min after injection of 18F-PFH. The plasma clearance of 18F-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 18F-PFH. Dynamic PET/CT studies were conducted in normal rats injected with 18F-PFH.
  
  
  RESULTS
  In normal rats, the plasma clearance of 18F-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 18F-PFH was found to associate with plasma proteins in vivo in normal rats. Biodistribution studies of 18F-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 18F-PFH indicated that it was excreted intact, with no metabolic products. Dynamic PET revealed a rapid clearance of 18F-PFH through the renal-urinary pathway. The PET-derived renograms revealed a time to peak activity of 3.0±1.0 min.
  
  
  CONCLUSIONS
  These combined results warrant further investigation of 18F-PFH as a radiopharmaceutical for the assessment of renal function by PET.
authors.affiliation: Department of Pharmaceutical Sciences, The University of Oklahoma College of Pharmacy, Oklahoma City, Oklahoma 73117, USA.
authors.forename: Vibhudutta
authors.initials: V
authors.lastname: Awasthi
authors.forename: Gopal
authors.initials: G
authors.lastname: Pathuri
authors.forename: Hrushikesh B
authors.initials: HB
authors.lastname: Agashe
authors.forename: Hariprasad
authors.initials: H
authors.lastname: Gali
mesh_terms: D000818:Animals; D004355:Drug Stability; D005260:Female; D005462:Fluorine Radioisotopes; D006626:Hippurates; D006801:Humans; D007553:Isotope Labeling; D007668:Kidney / Q000502:physiology*; D049268:Positron-Emission Tomography / Q000379:methods*; D019275:Radiopharmaceuticals / Q000737:chemistry; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D005462:Fluorine Radioisotopes; D006626:Hippurates; D019275:Radiopharmaceuticals