Positron-emission tomography molecular imaging of glia and myelin in drug discovery for multiple sclerosis

INTRODUCTION: Therapies acting on glial cells are being explored for new drug development for multiple sclerosis. Molecular imaging using positron-emission tomography (PET) could address relevant questions in early phase clinical trials. AREAS COVERED: In this article, the authors critically review human PET methods that can be applied in specialised centres for imaging activated microglia and astrocytes and myelin. EXPERT OPINION: Strengths of PET lie in the molecular selectivity, sensitivity and potential for absolute quantitation. Even now, translocator protein PET radioligands could be used in exploratory studies for interventions targeting brain microglial activation. The clinical and neuropathological meaningfulness of signal from PET radioligands reporting on astrocyte activation through cellular expression of either monoamine oxidase B or the I2-imidazoline receptor or metabolism of [(11)C]acetate can now explored. [(11)C] N-methyl-4,4'-diaminostilbene, a PET marker for myelin, could soon enter first human trials. However, use of any of these PET glial markers demands a well-focused hypothesis and a commitment to validation in the context of use. Enhanced access to these radioligands, standardisation of analyses and lowering the costs of using them are needed if their full promise is to be realised.