Illuminating Multiple Sclerosis: Next-Generation PET Tracers for Molecular Insights

: Molecular imaging is redefining in vivo characterization of multiple sclerosis, a demyelinating disease with complex and heterogeneous clinical profiles. Recent advances in PET tracers enable more specific detection of pathologic features beyond conventional MRI. Among them, [18F]3F4AP-a fluorinated analog of 4-aminopyridine-targets voltage-gated potassium channels that become exposed after demyelination, offering a promising tool to detect myelin loss. Similarly, [11C]PiB and [11C]MeDAS, originally developed for amyloid and myelin imaging, respectively, exhibit high affinity for myelin, allowing direct assessment of white matter integrity. In particular, [11C]MeDAS shows selective binding to intact myelin sheaths and strong correlation with histologic myelin content in preclinical models. These agents have demonstrated utility in both animal studies and early clinical investigations, supporting their translational relevance. This review focuses on the pharmacologic properties, imaging protocols, and developmental progress of PET tracers that directly or indirectly reflect demyelination, advancing personalized approaches to diagnosis, monitoring, and therapeutic evaluation in multiple sclerosis.