How Safe Is Gadobutrol? Examining the Effect of Gadolinium Deposition on the Nervous System

Abstract

This study aimed to evaluate the safety of gadobutrol, a gadolinium-based contrast agent used in medical imaging, by investigating its effect on the nervous system under physiological and inflammatory conditions. Male Sprague Dawley rats were divided randomly into four groups, including gadobutrol, saline, LPS + gadobutrol, and LPS + saline, and were given intraperitoneal injections of gadobutrol (2.5 mmol/kg) or saline for 20 days. Weekly sensorimotor and cognitive behavioral tests were performed over 4 weeks, and Gd concentration in nervous tissues was analyzed using inductively coupled plasma mass spectrometry (ICP-MS). Lactate dehydrogenase (LDH) activity was measured to evaluate cytotoxicity, and electromyography (EMG) recordings from the gastrocnemius muscle were also obtained to examine signal transmission in sciatic nerves. The results indicated that gadobutrol did not induce significant behavioral changes under normal conditions. However, when administered along with LPS, the combination led to behavioral dysfunction. ICP-MS analysis revealed a higher concentration of Gd in the cerebrum and spinal cord of gadobutrol + LPS-treated rats, while peripheral nerves showed lower concentrations. In addition, there was a significant increase in LDH activity in the hippocampus of the gadobutrol group. EMG responses to electrical stimulation of the sciatic nerve demonstrated a decreased threshold of nociceptive reflexes in the gadobutrol group. Overall, while gadobutrol may be considered safe under normal physiological conditions, the findings suggest that its safety may be compromised under inflammatory conditions.