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 [F]-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.

Cognitive function in amyotrophic lateral sclerosis: a cross-sectional and prospective pragmatic clinical study with review of the literature

“…The estimation of the risk for further cognitive decline contributes to the development of personalized symptom management plans for individuals with a disease for which no causal therapy is available yet. Neuroimaging techniques and other biomarkers could help to group in individuals with ALS according to their risk of cognitive impairment [ 66 – 68 ]. For instance, cognitive performance correlates with changes in diffusion tensor imaging (DTI) [ 69 ], while modified neuropsychological tests or alternative methods of cognitive testing, such as those with eye-tracker controlled or brain-computer interface [ 70 , 71 ], could be used to screen patients since the by-pass potential biases stemming from severe motor dysfunction.…”

PET Imaging for Oxidative Stress in Neurodegenerative Disorders Associated with Mitochondrial Dysfunction

“…Besides oxidative stress, many pathological molecular factors have been investigated using PET imaging in patients with ALS [ 147 , 148 ]. Interestingly, several PET studies to image neuroinflammation using TSPO radioligands, such as 11 C-( R )-PK11195, 18 F-DPA714, and 11 C-PBR28, showed increased uptake mainly in the primary motor cortex in ALS patients [ 149 , 150 , 151 , 152 ].…”

Multicenter validation of [18F]-FDG PET and support-vector machine discriminant analysis in automatically classifying patients with amyotrophic lateral sclerosis versus controls

“…Besides motor neuron degeneration, significant extra motor cerebral pathology has been observed. In up to 50% of cases, cognitive and/or behavioral impairment exists, with 10-15% of patients meeting the criteria of overt frontotemporal dementia (1)(2)(3)(4)(5). The clinical diagnosis of ALS is based on the presence of UMN and LMN involvement in different body areas in the absence of other pathologies.…”