Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease involving upper and lower motor neurons, extra-motor neurons, microglia and astrocytes. The neurodegenerative process results in progressive muscle paralysis and even in cognitive impairment. Within the complex diagnostic work-up, positron emission tomography (PET) represents a valuable imaging tool in the assessment of patients with ALS. PET, by means of different radiotracers (i.e. 18F-fluorodeoxyglucose, 6-[18F]fluoro-L-dopa, [11C]flumazenil) can assess the status of the wide range of brain regions and neural circuits, which can be affected by ALS. Furthermore, experimental radiocompounds have been developed for the evaluation of white matter, which plays a role in the progression of the disease. Here we present a comprehensive review including in different sections the most relevant PET studies: studies investigating ALS and ALS-mimicking conditions (especially primary lateral sclerosis and other neurodegenerative diseases), articles selecting specific subsets of patients (with bulbar or spinal onset), studies investigating patients with familial type of ALS, studies evaluating the role of the white matter in ALS and papers evaluating the diagnostic sensitivity of PET in ALS patients.
