Quantitative assessment of myelin density using [(11)C]MeDAS PET in patients with multiple sclerosis: a first-in-human study

PURPOSE: Multiple sclerosis (MS) is a disease characterized by inflammatory demyelinated lesions. New treatment strategies are being developed to stimulate myelin repair. Quantitative myelin imaging could facilitate these developments. This first-in-man study aimed to evaluate [(11)C]MeDAS as a PET tracer for myelin imaging in humans. METHODS: Six healthy controls and 11 MS patients underwent MRI and dynamic [(11)C]MeDAS PET scanning with arterial sampling. Lesion detection and classification were performed on MRI. [(11)C]MeDAS time-activity curves of brain regions and MS lesions were fitted with various compartment models for the identification of the best model to describe [(11)C]MeDAS kinetics. Several simplified methods were compared to the optimal compartment model. RESULTS: Visual analysis of the fits of [(11)C]MeDAS time-activity curves showed no preference for irreversible (2T3k) or reversible (2T4k) two-tissue compartment model. Both volume of distribution and binding potential estimates showed a high degree of variability. As this was not the case for 2T3k-derived net influx rate (K(i)), the 2T3k model was selected as the model of choice. Simplified methods, such as SUV and MLAIR2 correlated well with 2T3k-derived K(i), but SUV showed subject-dependent bias when compared to 2T3k. Both the 2T3k model and the simplified methods were able to differentiate not only between gray and white matter, but also between lesions with different myelin densities. CONCLUSION: [(11)C]MeDAS PET can be used for quantification of myelin density in MS patients and is able to distinguish differences in myelin density within MS lesions. The 2T3k model is the optimal compartment model and MLAIR2 is the best simplified method for quantification. Trial registration. NL7262. Registered 18 September 2018. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s00259-022-05770-4.