The use of Ga-EDTA PET allows detecting progressive decline of renal function in rats.

INTRODUCTION

Evaluation of glomerular filtration rate is very important in both preclinical and clinical setting, especially in the context of chronic kidney disease. It is typically performed using Cr-EDTA or by imaging with I-Hippuran scintigraphy, which has a significantly lower resolution and sensitivity as compared to PET. Ga-EDTA represents a valid alternative due to its quick availability using a Ge/Ga generator, while PET/CT enables both imaging of renal function and accurate quantitation of clearance of activity from both plasma and urine. Therefore, we aimed at investigating the use of Ga-EDTA as a preclinical tracer for determining renal function in a knock-in rat model known to present progressive decline of renal function.

METHODS

Ga-EDTA was injected in 23 rats, either wild type (n=10) or knock-in (n=13). By applying a unidirectional, two-compartment model and Rutland-Patlak Plot linear regression analysis, split renal function was determined from the age of 6 weeks to 12 months.

RESULTS

Glomerular filtration ranged from 0.025±0.01 ml/min at 6 weeks to 0.049±0.05 ml/min at 6 months in wild type rats. Glomerular filtration was significantly lower in knock-in rats at 6 and 12 months (P<0.01). No significant difference was observed in renal volumes between knock-in and wild type animals, based on imaging-derived volume calculations.

CONCLUSIONS

Ga-EDTA turned out to be a very promising PET/CT tracer for the evaluation of split renal function. This method allowed detection of progressive renal impairment in a knock-in rat model. Additional validation in a human cohort is warranted to further assess clinical utility in both, healthy individuals and patients with renal impairment.