Evaluation of glomerular kidney function with 68Ga-DTPA in small animal PET/CT (#109)
PET imaging is a powerful sensitive method in preclinical and clinical studies for assessing metabolic or pharmacological parameters. For pharmacokinetic studies the evaluation of kidney function is essential. One non-invasive technique for assessing the glomerular filtration rate (GFR) is SPECT imaging using the marker 99mTc-DTPA. The question of this study was to analyze whether 68Ga labeling of DTPA can be done with proper efficacy and can be used in in vivo PET studies.
Labeling of DTPA was realized with 68Ga eluted from SCX cartridges with 5 M NaCl/0.1 M HCl [1]. Experiments were performed in healthy rats (body weight 200-240 g). After labeling, 20 MBq of 68Ga-DTPA solution was injected into the lateral tail vein. Imaging was done with a nanoScan PET/CT (Mediso) over 60 min, with final CT and dynamic PET reconstruction. ROIs of kidneys, heart and bladder were analyzed in PET image series and time-activity curves were calculated. In addition biodistribution of the 68Ga-DTPA was analyzed ex vivo 2 min and 60 min after injection.
Efficacy of DTPA labeling with 68Ga was >98%, leading to 20 MBq tracer solution containing 0.15-0.2 M NaCl for an i.v. bolus. In PET studies the kidney TACs revealed a peak at 1.8±0.2 min (14±2%ID/g) with a t1/2 of 1.3±0.5 min and 6.5±0.95 min for the fast redistribution and slow elimination phase. The GFR was determined to be 0.2±0.1ml/min/100g bodyweight in healthy animals. The biodistribution experiments showed in blood
DTPA labeled with 68Ga leads to a reliable final product for the evaluation of GFR via small animal PET. The obtained renal clearance differed from data of 99mTc-DTPA in literature and therefore needs further investigation.
- [1] Dirk Mueller et al., “Radiolabeling of DOTA-like conjugated peptides with generator-produced 68Ga and using NaCl-based cationic elution method.”, Nature Protocols, 11, 1057–1066, (2016), doi:10.1038/nprot.2016.060