Diluted gadoteridol (ProHance®) causes mild ototoxicity in cochlear outer hair cells

Conclusion: Administration of diluted solutions of gadoteridol might cause considerably less toxic effects on cochlear outer hair cells (OHCs). Objectives: Visualization of endolymphatic hydrops is done by intratympanic injection of gadoliniumbased contrast agents (GBCAs) and three-dimensional fluid-attenuated inversion recovery (3-D FLAIR) magnetic resonance imaging. Here, we investigated the physiological and morphological responses of guinea pig cochlear cells to gadoteridol. Methods: Distortion product otoacoustic emission (DPOAE) levels were measured before and 1, 2, and 4 weeks after intratympanic injection of 1/8 or 1/16 dilution of gadoteridol in guinea pigs. Morphological changes in isolated cochlear OHCs were observed after application of gadoteridol and GdCl3. Results: At the highest frequency (F2 = 12 000 Hz), DPOAE level was significantly (p < 0.05) lower in the 1/8 diluted gadoteridol group than in the control group. Cell shape changes were observed in 24% (6/25) and 3% (1/33) of OHCs after application of 1/8 and 1/16 diluted gadoteridol, respectively. The occurrence of morphological damage was significantly lower after application of saline compared with 1/8 diluted gadoteridol. Morphological damage was significantly lower after application of 1/16 diluted gadoteridol compared with 1/8 diluted gadoteridol (p < 0.05). Morphological damage was observed at a high rate (8/10 cells, 80%) after application of GdCl3.