Nephrotoxicity in mice after repeated imaging using 111In-labeled peptides

J Nucl Med. 2010 Jun;51(6):973-7. doi: 10.2967/jnumed.109.074310. Epub 2010 May 19.

Abstract

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.

Conclusion: 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Exenatide
  • Female
  • Indium Radioisotopes*
  • Injections
  • Kidney / pathology
  • Kidney / physiopathology
  • Kidney / radiation effects*
  • Low Density Lipoprotein Receptor-Related Protein-2 / deficiency
  • Low Density Lipoprotein Receptor-Related Protein-2 / metabolism
  • Male
  • Mice
  • Organ Specificity
  • Pentetic Acid / chemistry
  • Peptides* / administration & dosage
  • Peptides* / chemistry
  • Radiation Dosage
  • Risk
  • Time Factors
  • Tomography, Emission-Computed, Single-Photon / adverse effects*
  • Tomography, X-Ray Computed
  • Venoms / chemistry

Substances

  • Indium Radioisotopes
  • Low Density Lipoprotein Receptor-Related Protein-2
  • Peptides
  • Venoms
  • Pentetic Acid
  • Exenatide