Evaluation of para-18F-fluorohippurate PET renography to predict future disease progression in a rat model of ADPKD

1077 Objectives Prognostic markers for progression of polycystic kidney disease are limited. Our objective for this pilot study was to evaluate the potential of early para-18F-fluorohippurate (18F-PFH) PET renography to predict future progression of disease in Han:SPRD rats1 with slowly progressive autosomal dominant polycystic kidney disease (ADPKD) . Methods Four groups (n = 2 to 7) of genotyped male and female cystic (Cy/+) and non-cystic (+/+) Han:SPRD rats underwent PET renography using 18F-PFH, a renal tubular agent,2,3 and blood sampling at ages 6 and 26 weeks. T2 and T20 values, which represent the percent of the injected dose of 18F-PFH in kidneys at 2 minutes and 20 minutes after injection, were determined from imaging data. The T20/T2 ratio was assessed as a prognostic marker. Rats were euthanized after renography at age 26 weeks, and kidney weight/body weight ratios (KW/BW%) were determined as a measure of PKD progression. Results Serum creatinine (S-Cr) and serum urea nitrogen (SUN) concentrations did not differ in female and male +/+ and Cy/+ rats at age 6 weeks, but they were significantly higher in Cy/+ than +/+ rats at age 26 weeks of age and male Cy/+ rats displayed significantly higher values than female Cy/+ rats. Importantly, male Cy/+ rats displayed higher T20/T2 values than female Cy/+ at age 6 weeks, which correlated with S-Cr, SUN, and KW/BW% at age 26 weeks, indicating that 18F-PFH PET at 6 weeks of age accurately predicted disease outcome at 26 weeks of age. Conclusions The results indicate that male Cy/+ rats exhibit more severe disease than female Cy/+ rats, which is consistent with literature reports in this model. This study indicates that T20/T2 ratio obtained from 18F-PFH PET renography could be used as a surrogate marker to predict disease progression at an early stage. Research Support This work was funded by an OU College of Pharmacy startup grant and the John S. Gammill Endowment for PKD Research.