Investigation of the ototoxicity of gadoteridol (ProHance) and gadodiamide (Omniscan) in mice

Acta Otolaryngol. 2016 Nov;136(11):1091-1096. doi: 10.1080/00016489.2016.1193892. Epub 2016 Jun 17.

Abstract

Conclusion: In the mouse, when a tympanic perforation is present, gadoteridol does not seem to cause ototoxicity. Gadodiamide may cause mild ototoxicity other than toxicity to the outer hair cells of the cochlea.

Objectives: Endolymphatic hydrops have been visualized through intra-tympanic injection of gadolinium-based contrast agents (GBCAs) and three-dimensional fluid-attenuated inversion recovery (3-D FLAIR) magnetic resonance imaging. However, reports on the safety of GBCAs are limited. This study aimed to assess ototoxicity of gadoteridol and gadodiamide.

Method: In a prospective, randomized, controlled trial, myringotomies in the left ear were performed in 20 male C57 BL/6 mice. After testing the baseline auditory brainstem response (ABR) (range = 8-32 kHz), the test solution (gadoteridol, gadodiamide, saline, or cisplatin) was injected into the left ear. ABR testing was repeated 14 days after test solution application. In morphological experiments, images of post-mortem surface preparations were assessed for cochlear hair cell status.

Results: At 14 days following gadoteridol application, there was no significant change in ABR thresholds at 8, 16, or 32 kHz. Gadodiamide application caused a significant change in the ABR threshold at 8 kHz. Apparent cochlear hair cell loss was not observed in the surface preparation after gadoteridol or gadodiamide application.

Keywords: Auditory brainstem response; MRI; gadodiamide; gadolinium-based contrast agent; gadoteridol; mouse; ototoxicity; surface preparation.

MeSH terms

  • Animals
  • Cochlea / drug effects*
  • Contrast Media / toxicity*
  • Evoked Potentials, Auditory, Brain Stem
  • Gadolinium / toxicity
  • Gadolinium DTPA / toxicity*
  • Heterocyclic Compounds / toxicity*
  • Male
  • Mice, Inbred C57BL
  • Organometallic Compounds / toxicity*
  • Random Allocation

Substances

  • Contrast Media
  • Heterocyclic Compounds
  • Organometallic Compounds
  • gadoteridol
  • gadodiamide
  • Gadolinium
  • Gadolinium DTPA