Assessing Glomerular Filtration in Small Animals Using [ 68 Ga]DTPA and [ 68 Ga]EDTA with PET Imaging.

PURPOSE: Determining the glomerular filtration rate (GFR) is essential for clinical medicine but also for pre-clinical animal studies. Functional imaging using positron emission tomography (PET) allows repetitive almost non-invasive measurements. The aim of the study was the development and evaluation of easily synthesizable PET tracers for GFR measurements in small animals.

PROCEDURES: Diethylenetriaminepentaacetic acid (DTPA) and ethylenediaminetetraacetic acid (EDTA) were labeled with Ga-68. The binding to blood cells and plasma proteins was tested in vitro. The distribution of the tracers in rats was analyzed by PET imaging and ex vivo measurements. From the time-activity-curve of the blood compartment (heart) and the total tracer mass excreted by the kidney, the GFR was calculated. These values were compared directly with the inulin clearance in the same animals.

RESULTS: Both tracers did not bind to blood cells. [68 Ga]DPTA but not [68 Ga]EDTA showed strong binding to plasma proteins. For this reason, [68 Ga]DPTA stayed much longer in the blood and only 30 % of the injected dose was eliminated by the kidney within 60 min whereas the excretion of [68 Ga]EDTA was 89 ± 1 %. The calculated GFR using [68 Ga]EDTA was comparable to the measured inulin clearance in the same animal. Using [68 Ga]-DPTA, the measurements led to values which were 80 % below the normal GFR. The results also revealed that definition of the volume of interest for the blood compartment affects the calculation and may lead to a slight overestimation of the GFR.

CONCLUSIONS: [68 Ga]EDTA is a suitable tracer for GFR calculation from PET imaging in small animals. It is easy to be labeled, and the results are in good accordance with the inulin clearance. [68 Ga]DTPA led to a marked underestimation of GFR due to its strong binding to plasma proteins and is therefore not an appropriate tracer for GFR measurements.