Recent Developments in Positron Emission Tomography Tracers for Proteinopathies Imaging in Dementia

Abstract

An early detection and intervention for dementia represent tremendous unmet clinical needs and priorities in society. A shared feature of neurodegenerative diseases causing dementia is the abnormal accumulation and spreading of pathological protein aggregates, which affect the selective vulnerable circuit in a disease-specific pattern. The advancement in positron emission tomography (PET) biomarkers has accelerated the understanding of the disease mechanism and development of therapeutics for Alzheimer’s disease and Parkinson’s disease. The clinical utility of amyloid-β PET and the clinical validity of tau PET as diagnostic biomarker for Alzheimer’s disease continuum have been demonstrated. The inclusion of biomarkers in the diagnostic criteria has introduced a paradigm shift that facilitated the early and differential disease diagnosis and impacted on the clinical management. Application of disease-modifying therapy likely requires screening of patients with molecular evidence of pathological accumulation and monitoring of treatment effect assisted with biomarkers. There is currently still a gap in specific 4-repeat tau imaging probes for 4-repeat tauopathies and α-synuclein imaging probes for Parkinson’s disease and dementia with Lewy body. In this review, we focused on recent development in molecular imaging biomarkers for assisting the early diagnosis of proteinopathies (i.e., amyloid-β, tau, and α-synuclein) in dementia and discussed future perspectives.

Synthesis and Evaluation of 18F-Labeled Chalcone Analogue for Detection of α-Synuclein Aggregates in the Brain Using the Mouse Model

“…To date, in preclinical studies, few probes have been reported to detect α-syn aggregates in vivo using an inoculated mouse model . In this experiment, [ 18 F]­FHCL-2 recognized α-syn aggregates inoculated in the mouse brain, suggesting that 18 F-labeled chalcone analogues might be new ligands for in vivo α-syn imaging.…”

“…[ 18 F]­C05-05, known as the C05 series, also depicted α-syn aggregates in vivo in the preclinical stage, and further research, including clinical studies, is expected. Thus, promising probes have been reported; however, no successful in vivo imaging of α-syn aggregates has been reported in the clinical stage, and α-syn-targeted probes are still under development worldwide …”

Molecular imaging biomarkers in familial frontotemporal lobar degeneration: Progress and prospects

“…Even though more and more tracers were approved by the US Food and Drug Administration and by the European Medicines Agency for clinical usage ( 106 ), the higher cost and longer acquisition times compared to MRI might limit the wide applications in clinical practice ( 107 ). Changes in the levels of human fluid components could reflect underlying pathophysiological processes, and several fluid biomarkers were available or showed potential values such as Aβ, tau, NfL, and progranulin.…”

Fission Impossible: Stabilized miRNA-Based Analogs in Neurodegenerative Disease

“…The essential neuro-pathological features of AD have been known for almost ~120 years, and currently the presence and abundance of pathological lipoprotein-rich aggregates including amyloid-beta (Aβ) peptide-enriched “senile plaques” (SP) and the accumulation of abnormally hyper-phosphorylated tau (pTau) proteins into twisted neurofilament bundles known as neurofibrillary tangles (NFT) in the AD affected neocortex and hippocampus are still required for an accurate pathological diagnosis of AD at post-mortem examination of the brain (Alzheimer et al, 1995 ; DeTure and Dickson, 2019 ). Recent developments and advancements in RNA sequencing technologies and molecular imaging involving specialized positron emission tomography (PET)-based technologies and the use of multiple biofluid biomarkers have become increasingly useful for assisting in the early diagnosis, prognosis, prediction of time-to-symptom onset and drug treatment-monitoring of complex lipoproteinopathies including AD (Swarbrick et al, 2019 ; Shi et al, 2020 ; Wei et al, 2020 ; Zhao et al, 2020 ; Beach and Malek-Ahmadi, 2021 ; Ni and Nitsch, 2022 ; Ogonowski et al, 2022 ).…”