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Positron emission tomography in amyotrophic lateral sclerosis: Towards targeting of molecular pathological hallmarks

Abstract

During the past decades, extensive efforts have been made to expand the knowledge of amyotrophic lateral sclerosis (ALS). However, clinical translation of this research, in terms of earlier diagnosis and improved therapy, remains challenging. Since more than 30% of motor neurons are lost when symptoms become clinically apparent, techniques allowing non-invasive, in vivo detection of motor neuron degeneration are needed in the early, pre-symptomatic disease stage. Furthermore, it has become apparent that non-motor signs play an important role in the disease and there is an overlap with cognitive disorders, such as frontotemporal dementia (FTD). Radionuclide imaging, such as positron emission tomography (PET) and single-photon emission computed tomography (SPECT), form an attractive approach to quantitatively monitor the ongoing neurodegenerative processes. Although [18F]-FDG has been recently proposed as a potential biomarker for ALS, active targeting of the underlying pathologic molecular processes is likely to unravel further valuable disease information and may help to decipher the pathogenesis of ALS. In this review, we provide an overview of radiotracers that have already been applied in ALS and discuss possible novel targets for in vivo imaging of various pathogenic processes underlying ALS onset and progression.

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Correspondence to Stefanie M. A. Willekens.

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PVD and KVL hold a senior clinical investigator ship from FWO-Vlaanderen. PVD is supported by grants from the Opening the Future Fund (KU Leuven), the Interuniversity Attraction Poles (IUAP) program P7/16 of the Belgian Federal Science Policy Office, the Alzheimer Research Foundation (SAO-FRA), the Flemish government-initiated Flanders Impulse Program on Networks for Dementia Research (VIND), the Fund for Scientific Research Vlaanderen (FWO-Vlaanderen), under the frame of E-RARE-2 (PYRAMID) and JPND (STRENGTH and RiMod-FTD), the IWT, the ALS liga België and the Thierry Latran foundation. For ALS and neuroinflammation research, KVL is supported by the European Union’s Seventh Framework Programme (FP7/2007–2013) under Grant Agreement no. HEALTH-F2-2011-278850 (INMiND).

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All authors declare that they have no conflicts of interest.

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Willekens, S.M.A., Van Weehaeghe, D., Van Damme, P. et al. Positron emission tomography in amyotrophic lateral sclerosis: Towards targeting of molecular pathological hallmarks. Eur J Nucl Med Mol Imaging 44, 533–547 (2017). https://doi.org/10.1007/s00259-016-3587-y

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Keywords

  • ALS
  • Neurodegeneration
  • PET
  • Targets
  • Radiotracers