Evaluation of [18F]PFH PET renography to predict future disease progression in a rat model of autosomal dominant polycystic kidney disease

Abstract

IntroductionPrognostic markers for progression of polycystic kidney disease (PKD) are limited. We evaluated the potential of early para-[18F]fluorohippurate ([18F]PFH) positron emission tomography (PET) renography to predict future progression of PKD in Han:SPRD rats with slowly progressive autosomal dominant PKD. Materials and methodsMale and female heterozygous (Cy/+) and normal littermate (+/+) Han:SPRD rats underwent [18F]PFH PET renography and blood sampling to measure serum creatinine (S-Cr) and serum urea nitrogen (SUN) concentrations at 6 and 26wk of age. T2 and T20 values, which represent the percent of the injected dose of [18F]PFH in kidneys at 2 and 20min after injection, were determined from imaging data. T20/T2 ratio was assessed as a prognostic marker. Rats were euthanized after renography at 26wk of age, and kidney weight/body weight ratios (KW/BW%) were determined as a measure of PKD progression. ResultsMale 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 6wk of age, but they were higher at 26wk 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 6wk of age. Importantly, male Cy/+ rats displayed higher T20/T2 ratios than female Cy/+ rats. T20/T2 ratios obtained at 6wk of age correlated well with S-Cr, SUN, and KW/BW% values obtained at 26wk of age. ConclusionsThis study indicates that T20/T2 ratio derived from [18F]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.