A systematic review of lessons learned from PET molecular imaging research in atypical parkinsonism

Abstract

PurposeTo systematically review the previous studies and current status of positron emission tomography (PET) molecular imaging research in atypical parkinsonism.MethodsMEDLINE, ISI Web of Science, Cochrane Library, and Scopus electronic databases were searched for articles published until 29th March 2016 and included brain PET studies in progressive supranuclear palsy (PSP), multiple system atrophy (MSA), and corticobasal syndrome (CBS). Only articles published in English and in peer-reviewed journals were included in this review. Case-reports, reviews, and non-human studies were excluded.ResultsSeventy-seven PET studies investigating the dopaminergic system, glucose metabolism, microglial activation, hyperphosphorilated tau, opioid receptors, the cholinergic system, and GABAA receptors in PSP, MSA, and CBS patients were included in this review. Disease-specific patterns of reduced glucose metabolism have shown higher accuracy than dopaminergic imaging techniques to distinguish between parkinsonian syndromes. Microglial activation has been found in all forms of atypical parkinsonism and reflects the known distribution of neuropathologic changes in these disorders. Opioid receptors are decreased in the striatum of PSP and MSA patients. Subcortical cholinergic dysfunction was more severe in MSA and PSP than Parkinson’s disease patients although no significant changes in cortical cholinergic receptors were seen in PSP with cognitive impairment. GABAA receptors were decreased in metabolically affected cortical and subcortical regions in PSP patients.ConclusionsPET molecular imaging has provided valuable insight for understanding the mechanisms underlying atypical parkinsonism. Changes at a molecular level occur early in the course of these neurodegenerative diseases and PET imaging provides the means to aid differential diagnosis, monitor disease progression, identify of novel targets for pharmacotherapy, and monitor response to new treatments.

Recent advances in neuropathology, biomarkers and therapeutic approach of multiple system atrophy

“…Conventional imaging modalities (ie, CT and MRI) and molecular and functional imaging have been used in the differential diagnosis of MSA (reviewed in ref 57). Hypometabolism, decreased activity of dopaminergic and cholinergic systems, and neuroinflammation have been visualised in brain regions vulnerable to MSA (table 2).…”

Role of Neuroimaging on Differentiation of Parkinson’s Disease and Its Related Diseases

“…In recent decades, positron emission computed tomography (PET) molecular imaging has provided a better understanding of the pathophysiological mechanisms underlying atypical parkinsonism. 19 However, PET typically depends on an adjacent cyclotron. Thus, the availability of single photon emission computed tomography (SPECT) is generally greater than that of PET.…”

Synthesis of [11C]HG-10-102-01 as a new potential PET agent for imaging of LRRK2 enzyme in Parkinson’s disease

“…8,9 Advanced biomedical imaging technique positron emission tomography (PET) is a promising modality for PD, and significant advances have accomplished in this field of molecular imaging. 10 The representative PET tracers used in PD imaging such as [ 18 F]FDOPA for dopamine synthesis, [ 11 C]-CFT for dopamine transporter, [ 11 C]DTBZ for vesicular monoamine transporter type 2, [ 11 C]raclopride for D 2 receptor, [ 11 C]WAY100635 for serotonin receptor, [ 11 C]PBR28 for translocator protein, [ 11 C]PIB for aggregated -amyloid plaques, and [ 18 F]T807 ([ 18 F]AV-1451) for tau protein are listed in Figure 1. [11][12][13][14][15][16] The development of new PET imaging probes for in vivo detection of PD is critical for early and accurate diagnosis and for the successful discovery of diseasemodifying or neuro-protective therapies, as currently only symptomatic treatment is available.…”