Probes For PET Imaging Of Myelin

The loss of myelin, the insulation around many nerve cells in the brain, is a common cause of neurodegenerative disorders such as multiple sclerosis. Magnetic resonance imaging is the most common method for detecting lesions in the brain. Lesions detected by MRI may be caused not only by demyelination but also by inflammation, limiting the use of MRI for accurate diagnosis and therapeutic evaluation in MS. With appropriate myelin-specific probes, positron emission tomography could identify whether lesions observed by MRI are actually caused by demyelination. Yanming Wang of Case Western Reserve University, in Cleveland, and coworkers report preliminary evaluations of derivatives of 4,4′-diamino-trans-stilbene as PET imaging probes to detect demyelination (J. Med. Chem., DOI: 10.1021/jm8003637). Several of these probes, including a ¹²⁵I-radiolabeled probe (shown), cross the mouse blood-brain barrier and bind with high affinity and specificity to myelinated regions in the brain. Animal studies also showed that doses up to 80 mg/kg could be administered to mice with no toxic effects. Such doses are several orders of magnitude higher than what would be needed for imaging studies.