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


OBJECTIVE
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.


METHODS
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.
a Department of Otolaryngology , Aichi Medical University , Aichi , Japan.
Hiroshi
H
Nonoyama
a Department of Otolaryngology , Aichi Medical University , Aichi , Japan.
Tohru
T
Tanigawa
b Department of Cardiology , Nagoya University Graduate School of Medicine , Nagoya , Japan.
Rei
R
Shibata
a Department of Otolaryngology , Aichi Medical University , Aichi , Japan.
Hirokazu
H
Tanaka
a Department of Otolaryngology , Aichi Medical University , Aichi , Japan.
Nobuyuki
N
Katahira
a Department of Otolaryngology , Aichi Medical University , Aichi , Japan.
Yuichiro
Y
Horibe
c Department of Otolaryngology , Nagoya City University , Nagoya , Japan.
Keiji
K
Takemura
d Division of Biostatistics , Clinical Research Center, Aichi Medical University , Aichi , Japan.
Kenta
K
Murotani
e Department of Anatomy , Aichi Medical University , Aichi , Japan.
Norio
N
Ozeki
a Department of Otolaryngology , Aichi Medical University , Aichi , Japan.
Hiromi
H
Ueda
D000818:Animals; D003051:Cochlea / Q000187:drug effects*; D003287:Contrast Media / Q000633:toxicity*; D016057:Evoked Potentials, Auditory, Brain Stem; D005682:Gadolinium / Q000633:toxicity; D019786:Gadolinium DTPA / Q000633:toxicity*; D006571:Heterocyclic Compounds / Q000633:toxicity*; D008297:Male; D008810:Mice, Inbred C57BL; D009942:Organometallic Compounds / Q000633:toxicity*; D011897:Random Allocation
D003287:Contrast Media; D006571:Heterocyclic Compounds; D009942:Organometallic Compounds; C062402:gadoteridol; C064925:gadodiamide; D005682:Gadolinium; D019786:Gadolinium DTPA
Auditory brainstem response; MRI; gadodiamide; gadolinium-based contrast agent; gadoteridol; mouse; ototoxicity; surface preparation