Combined in vivo PET imaging of astrogliosis and tau facilitates differential diagnosis of parkinsonian syndromes in correlation with the phenotype

Ziel/Aim:

Neurodegenerative parkinsonian syndromes comprise a number of disorders that are grouped together due to similar clinical features but are separated on the basis of different pathologies (alpha-synuclein or tau protein). Due to the overlap of signs and symptoms a precise differentiation is often difficult. Enormous efforts have been taken to develop tau-selective PET imaging agents, but strong off-target binding to MAO-B has been observed across first generation ligands. Nonetheless, astrogliosis related MAO-B elevation is a common histopathological known feature of all parkinsonian syndromes and might be itself an interesting imaging target. Therefore, this study aimed to investigate the performance of F-18-THK5351 for differential diagnosis of parkinsonian syndromes.

Methodik/Methods:

F-18-THK5351-PET was performed in 35 patients (6 Parkinson's disease (PD), 9 multiple system atrophy with predominant parkinsonism (MSA-P), 6 MSA with predominant cerebellar ataxia (MSA-C), 14 progressive supranuclear palsy (PSP) Richardson's syndrome). Volume-of-interest based quantification of standardized-uptake-values was conducted in different parkinsonian syndrome related target regions. PET results were subjected to a multinomial logistic regression to determine the best predictor of diagnosis.

Ergebnisse/Results:

Elevated F-18-THK5351 uptake in midbrain and diencephalon differentiated PSP patients from PD and MSA-C. MSA-C patients were distinguishable by high tracer uptake in the pons and the cerebellar deep white matter when compared to PSP and PD patients, whereas MSA-P patients tended to show higher tracer uptake in the lentiform nucleus. Logistic regression models with regional tracer uptake resulted in an area under the curve of 0.98 for discrimination of tau- and alpha-synucleinopathies, and classified 34/35 patients into the correct diagnosis group.

Schlussfolgerungen/Conclusions:

The current study demonstrates that combined MAO-B and tau binding of F-18-THK5351 facilitates excellent differential diagnosis of parkinsonian syndromes. Uptake levels in the diencephalon, midbrain, pons and cerebellar deep white matter are useful predictors of diagnosis.