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

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
• gadolinium-based contrast agent
• gadoteridol
• gadodiamide
• MRI
• mouse
• ototoxicity
• surface preparation

Disclosure statement

The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper.