Nephrotoxicity in mice after repeated imaging using 111In-labeled peptides.
We determined the renal radiation dose of a series of (111)In-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 (111)In-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
Because of high renal retention, (111)In-diethylenetriaminepentaacetic 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.


CONCLUSIONS
Micro-SPECT enables longitudinal studies in 1 animal. However, long-term nephrotoxic effects may be induced after high renal radiation doses, even with (111)In-labeled radiotracers.
Melis
Marleen
M
Department of Nuclear Medicine, Erasmus MC Rotterdam, Rotterdam, The Netherlands. m.melis@erasmusmc.nl
Vegt
Erik
E
Konijnenberg
Mark W
MW
de Visser
Monique
M
Bijster
Magda
M
Vermeij
Marcel
M
Krenning
Eric P
EP
Boerman
Otto C
OC
de Jong
Marion
M
D000818:Animals; D000077270:Exenatide; D005260:Female; D007205:Indium Radioisotopes; D007267:Injections; D007668:Kidney / Q000473:pathology / Q000503:physiopathology / Q000528:radiation effects*; D026561:Low Density Lipoprotein Receptor-Related Protein-2 / Q000172:deficiency / Q000378:metabolism; D008297:Male; D051379:Mice; D009928:Organ Specificity; D004369:Pentetic Acid / Q000737:chemistry; D010455:Peptides / Q000008:administration & dosage / Q000737:chemistry; D011829:Radiation Dosage; D012306:Risk; D013997:Time Factors; D015899:Tomography, Emission-Computed, Single-Photon / Q000009:adverse effects*; D014057:Tomography, X-Ray Computed; D014688:Venoms / Q000737:chemistry
D007205:Indium Radioisotopes; D026561:Low Density Lipoprotein Receptor-Related Protein-2; D010455:Peptides; D014688:Venoms; D004369:Pentetic Acid; D000077270:Exenatide