The use of ⁶⁸Ga-EDTA PET allows detecting progressive decline of renal function in rats

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 ⁵¹Cr-EDTA or by imaging with ¹²³I-Hippuran scintigraphy, which has a significantly lower resolution and sensitivity as compared to PET. ⁶⁸Ga-EDTA represents a valid alternative due to its quick availability using a ⁶⁸Ge/⁶⁸Ga 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 ⁶⁸Ga-EDTA as a preclinical tracer for determining renal function in a knock-in rat model known to present progressive decline of renal function.

⁶⁸Ga-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.

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.

⁶⁸Ga-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.