Journal: Journal of the American Chemical Society
Authors: Luca Frullano*, Changning Wang*, Robert H. Miller**, and Yanming Wang*
Affiliation: *Division of Radiopharmaceutical Science, Case Center for Imaging Research, Department of Radiology, and **Department of Neuroscience, Case Western Reserve University
Artistic rendering of the applications of MIC
Myelin sheaths that cover nerve cells are an important part of a vertebrate’s nervous system. They allow for the fast transmission of nerve impulses. Multiple sclerosis (MS) and leukodystrophies are the result of abnormalities in or the destruction of myelin. In order to diagnose and treat these diseases it is important to determine the amount of myelin in the body.
Magnetic resonance imaging (MRI) has been used to diagnose and monitor these diseases; however, one drawback to MRI is interference due to the presence of water. Because of this interference the FDA has not approved MRI as the primary method to monitor MS and other myelin related diseases.
If MRI is to become a highly accurate method of myelin detection, a sensitive imaging agent must to be developed. The researchers mentioned other work previously published involving a compound, known to stain myelin, Luxol Fast Blue (LFB). Unfortunately, it was found that LFB is only moderately water-soluble and it cannot easily enter tissues. Therefore, the researchers proposed the synthesis of a small-molecule gadolinium-based imaging agent, MIC, for myelin that could reasonably be used clinically.
The authors synthesized MIC, as shown in the figure above. In addition to having a magnetic signal, MIC is also fluorescent. The researchers studied the ability of MIC to bind to myelin in the brains of mice using MIC’s fluorescent properties. MIC was shown to selectively bind to myelin. Once this was determined, the researchers used wild-type mice and mice with a genetic myelin deficiency to study MIC’s ability as a MRI contrast agent. They determined that the contrast was dependent on the concentration of myelin, indicating that MIC acted as a contrast agent.
Further work will delve into the mechanism by which MIC binds to myelin. Studies of the distribution of MIC in animals and the pharmacokinetics of MIC are also planned.