The Use of 68Ga-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-51 EDTA or by imaging with I-123-Hippuran scintigraphy, which has a significantly lower resolution and sensitivity as compared to PET. Ga-68-EDTA represents a valid alternative due to its quick availability using a Ge-68/Ga-68 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-68-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-68-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-68 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.