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

Abstract

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 [¹¹C]acetate can now explored. [¹¹C] 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.

Keywords:

• astrocytes
• drug development
• imaging
• microglia
• myelin
• positron-emission tomography
• radioligand

Acknowledgement

The authors acknowledge Mrs Lily Safra for personal support.

Declaration of interest

The authors acknowledge support from the Imperial College Healthcare Trust Biomedical Research Centre for their research. PM Matthews holds stocks in GlaxoSmithKline and receives research support from this company, as well as Biogen IDEC. He also receives research support from the UK Medical Research Council, the MS Society of Great Britain and the Progressive MS Alliance. He has also received recent honoraria from BiogenIDEC and Novartis. The authors also gratefully appreciate the support from Edmond J Safra Foundation. G Datta is funded through training grants from the Wellcome Trust and GlaxoSmithKline, Ltd that are administered by Imperial College London as part of an internal, competitive clinical scientist training programme. The authors also gratefully appreciate the support from Edmond J Safra Foundation. The authors have no other relevant affiliations or financial involvement with any organisation or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Notes

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