Nephrotoxicity in Mice After Repeated Imaging Using 111In-Labeled Peptides

We determined the renal radiation dose of a series of 111In-labeled peptides using animal SPECT. Because the animals’ health deteriorated, renal toxicity was assessed. Methods: Wild-type and megalin-deficient mice were imaged repeatedly at 3- to 6-wk intervals to quantify renal retention after injection of 40–50 MBq of 111In-diethylenetriaminepentaacetic acid– labeled peptides (octreotide, exendin, octreotate, neurotensin, and minigastrin analogs), and the absorbed kidney radiation doses were estimated. Body weight, renal function parameters, and renal histology were determined at 16–20 wk after the first scan and compared with those in naive animals. Results: Be-cause of high renal retention, 111In-diethylenetriaminepentaace-tic acid–exendin-4 scans resulted in a 70-Gy kidney radiation dose in wild-type mice. Megalin-deficient kidneys received 20– 40 Gy. The other peptides resulted in much lower renal doses. Kidney function monitoring indicated renal damage in imaged animals.Conclusion:Micro-SPECT enables longitudinal studies in 1 animal. However, long-term nephrotoxic effects may be in-duced after high renal radiation doses, even with 111In-labeled radiotracers. Key Words: nephrotoxicity; 111In; renal reabsorption; radiola-beled peptide; dosimetr