Opportunities for Molecular Imaging in Multiple Sclerosis Management: Linking Probe to Treatment

Imaging has been a critical component of multiple sclerosis (MS) management for nearly 40 years. The visual information derived from structural MRI, that is, signs of blood-brain barrier disruption, inflammation and demyelination, and brain and spinal cord atrophy, are the primary metrics used to evaluate therapeutic efficacy in MS. The development of targeted imaging probes has expanded our ability to evaluate and monitor MS and its therapies at the molecular level. Most molecular imaging probes evaluated for MS applications are small molecules initially developed for PET, nearly half of which are derived from U.S. Food and Drug Administration-approved drugs and those currently undergoing clinical trials. Superparamagnetic and fluorinated particles have been used for tracking circulating immune cells (in situ labeling) and immunosuppressive or remyelinating therapeutic stem cells (ex vivo labeling) clinically using proton (hydrogen 1 [¹H]) and preclinically using fluorine 19 (¹⁹F) MRI. Translocator protein PET and ¹H MR spectroscopy have been demonstrated to complement imaging metrics from structural (gadolinium-enhanced) MRI in nine and six trials for MS disease-modifying therapies, respectively. Still, despite multiple demonstrations of the utility of molecular imaging probes to evaluate the target location and to elucidate the mechanisms of disease-modifying therapies for MS applications, their use has been sparse in both preclinical and clinical settings.