title: Evaluation of [¹⁸F]PFH PET renography to predict future disease progression in a rat model of autosomal dominant polycystic kidney disease.
abstract: BACKGROUND
  Prognostic markers for progression of polycystic kidney disease (PKD) are limited. We evaluated the potential of early para-[(18)F]fluorohippurate ([(18)F]PFH) positron emission tomography (PET) renography to predict future progression of PKD in Han:SPRD rats with slowly progressive autosomal dominant PKD.
  
  
  METHODS
  Male and female heterozygous (Cy/+) and normal littermate (+/+) Han:SPRD rats underwent [(18)F]PFH PET renography and blood sampling to measure serum creatinine (S-Cr) and serum urea nitrogen (SUN) concentrations at 6 and 26 wk of age. T2 and T20 values, which represent the percent of the injected dose of [(18)F]PFH in kidneys at 2 and 20 min after injection, were determined from imaging data. T20/T2 ratio was assessed as a prognostic marker. Rats were euthanized after renography at 26 wk of age, and kidney weight/body weight ratios (KW/BW%) were determined as a measure of PKD progression.
  
  
  RESULTS
  Male and female Cy/+ rats are known to manifest PKD of different severity, male Cy/+ rats display much more severe PKD than female rats. S-Cr and SUN concentrations did not differ between +/+ and Cy/+ rats and between female and male Cy/+ rats at 6 wk of age, but they were higher at 26 wk of age and male rats displayed higher values than female rats, which indicates inability of S-Cr and SUN to measure disease severity at an early stage. T20/T2 ratios were higher for Cy/+ than +/+ rats at 6 wk of age. Importantly, male Cy/+ rats displayed higher T20/T2 ratios than female Cy/+ rats. T20/T2 ratios obtained at 6 wk of age correlated well with S-Cr, SUN, and KW/BW% values obtained at 26 wk of age.
  
  
  CONCLUSIONS
  This study indicates that T20/T2 ratio derived from [(18)F]PFH PET renography at an early age could be useful as a novel prognostic marker to predict future disease severity in a rat model of ADPKD.
authors.affiliation: Department of Pharmaceutical Sciences, College of Pharmacy, The University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA.
authors.forename: Gopal
authors.initials: G
authors.lastname: Pathuri
authors.affiliation: Department of Pharmaceutical Sciences, College of Pharmacy, The University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA.
authors.forename: Andria F
authors.initials: AF
authors.lastname: Hedrick
authors.affiliation: Department of Pharmaceutical Sciences, College of Pharmacy, The University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA.
authors.forename: Vibhudutta
authors.initials: V
authors.lastname: Awasthi
authors.affiliation: Nephrology Section, Department of Internal Medicine, College of Medicine, The University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA.
authors.forename: Benjamin D
authors.initials: BD
authors.lastname: Cowley
authors.affiliation: Department of Pharmaceutical Sciences, College of Pharmacy, The University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA. Electronic address: hgali@ouhsc.edu.
authors.forename: Hariprasad
authors.initials: H
authors.lastname: Gali
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D018450:Disease Progression; D005260:Female; D005462:Fluorine Radioisotopes; D006579:Heterozygote; D006626:Hippurates; D008297:Male; D016891:Polycystic Kidney, Autosomal Dominant / Q000000981:diagnostic imaging* / Q000235:genetics; D049268:Positron-Emission Tomography; D011866:Radioisotope Renography; D051381:Rats
chemical_list: C541416:4-fluorohippuric acid; D005462:Fluorine Radioisotopes; D006626:Hippurates
keywords: ADPKD; PET; Para-[(18)F]fluorohippurate; Prognostic biomarker; Renography