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  • Review Article
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Positron emission tomography in multiple sclerosis — straight to the target

Nature Reviews Neurology volume 17, pages 663–675 (2021)Cite this article

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Abstract

Following the impressive progress in the treatment of relapsing–remitting multiple sclerosis (MS), the major challenge ahead is the development of treatments to prevent or delay the irreversible accumulation of clinical disability in progressive forms of the disease. The substrate of clinical progression is neuro-axonal degeneration, and a deep understanding of the mechanisms that underlie this process is a precondition for the development of therapies for progressive MS. PET imaging involves the use of radiolabelled compounds that bind to specific cellular and metabolic targets, thereby enabling direct in vivo measurement of several pathological processes. This approach can provide key insights into the clinical relevance of these processes and their chronological sequence during the disease course. In this Review, we focus on the contribution that PET is making to our understanding of extraneuronal and intraneuronal mechanisms that are involved in the pathogenesis of irreversible neuro-axonal damage in MS. We consider the major challenges with the use of PET in MS and the steps necessary to realize clinical benefits of the technique. In addition, we discuss the potential of emerging PET tracers and future applications of existing compounds to facilitate the identification of effective neuroprotective treatments for patients with MS.

Key points

  • PET enables direct in vivo measurement of key processes in the pathogenesis of neurodegeneration in multiple sclerosis (MS).

  • PET imaging of neuroinflammatory processes has shown that innate immune cell activation inside and outside visible lesions is a relevant pathogenic mechanism in MS, even in the earliest stages of the disease.

  • Novel PET tracers that specifically target innate immune cells, lymphocytes, metabolic pathways, endothelial molecules and active astrocytes could provide new insights into the role of inflammation in neurodegeneration in MS.

  • PET imaging of myelin in patients with MS has shown that myelin loss and failure of myelin repair can contribute to the accumulation of clinical disability.

  • PET imaging of the mitochondria and synaptic vesicles can be used to detect the earliest metabolic and structural changes in neurons in MS.

  • PET imaging of pathological processes could provide robust outcome measures in clinical trials of drugs designed to delay or prevent neurodegeneration in MS.

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Fig. 1: PET targets in multiple sclerosis.
Fig. 2: PET imaging of neuroinflammation.
Fig. 3: PET imaging of demyelination and remyelination.
Fig. 4: PET imaging of neurodegeneration.

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Acknowledgements

The studies discussed that were performed in the Paris Brain Institute received funding from: ANR (Agence Nationale de la Recherche; grant MNP2008-007125); CEA (Commissariat aux Energies Atomiques); European Committee for Treatment and Research in MS (ECTRIMS); ELA (European Leukodystrophy Association; grant 2007-0481); ARSEP Foundation (Fondation pour l’aide à la recherche sur la sclérose en plaques); FRM (Fondation pour la Recherche Médicale); INSERM-DHOS (grant 2008–recherche clinique et translationnelle); Investissements d’avenir (grant ANR-10-IAIHU-06); JNLF (Journées de Neurologie de Langue Française); Programme Hospitalier de Recherche Clinique (PHRC national, 2010; APHP). APHP (Assistance Publique des Hôpitaux de Paris) sponsored these clinical studies. The authors are grateful to the Bouvet-Labruyère family for their constant support of our research projects. The authors thank the members of the CIC (Clinical Investigation Center; C. Louapre, J.C. Corvol) and CENIR (Centre de NeuroImagerie de l’ICM; S. Lehericy, E. Bardinet) in the Paris Brain Institute, and members of the SHFJ (Service Hospitalier Frédéric Joliot, Commissariat aux Energies atomiques; M. Bottlaender, B. Kunhast, P. Gervais, V. Lebon) for their invaluable contribution to the authors’ clinical studies and for their technical support. We also thank B. Dubois and the Scientific Committee of the INSIGHT study for kindly providing the 18F-florbetapir PET image. The authors are grateful to C. Fumat and C. Théry for their contribution to the conception and the realization of Fig. 1.

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Authors and Affiliations

  1. Sorbonne Université, Paris Brain Institute, ICM, CNRS, Inserm, Paris, France

    Benedetta Bodini, Matteo Tonietto & Bruno Stankoff

  2. Neurology Department, St. Antoine Hospital, APHP, Paris, France

    Benedetta Bodini & Bruno Stankoff

  3. Université Paris-Saclay, CEA, CNRS, Inserm, BioMaps, Service Hospitalier Frédéric Joliot, Orsay, France

    Matteo Tonietto

  4. Turku PET Centre, Division of Clinical Neurosciences, Turku University Hospital and University of Turku, Turku, Finland

    Laura Airas

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  1. Benedetta Bodini
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Bodini, B., Tonietto, M., Airas, L. et al. Positron emission tomography in multiple sclerosis — straight to the target. Nat Rev Neurol 17, 663–675 (2021). https://doi.org/10.1038/s41582-021-00537-1

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