Tau PET in Parkinson syndromes. A new diagnostic tool?

Tau PET in Parkinson syndromes. A new diagnostic tool?Jochen Hammes,1 Gérard Bischof,1,2 Kathrin Giehl,1 Özgür Onur,3 Alexander Drzezga,1,4 Thomas Klockgether,4 Thilo van Eimeren1,2,3,41) Multimodal Neuroimaging Group, Department of Nuclear Medicine, University of Cologne, Germany2) Cognitive Neuroscience, Institute of Neuroscience and Medicine (INM-3), Research Center Jülich, Germany3) Department of Neurology, University Hospital Cologne, Cologne, Germany4) German Centre for Neurodegenerative Diseases (DZNE), Bonn, GermanyObjectiveTo explore the potential of [F-18]-AV-1451 PET as a diagnostic tool in Parkinson plus syndromes.BackgroundClinically, atypical Parkinson syndromes are often difficult to separate from idiopathic Parkinson’s disease (iPD). However, there are marked differences in terms of underlying pathology and treatment response. Corticobasal syndrome (CBS) and progressive supranuclear palsy (PSP) are associated with pathological intracellular accumulation of tau protein, whereas the underlying pathology in multiple system atrophy (MSA) and iPD are not associated with tau pathology. [F-18]-AV-1451 (f.k.a. T807) is a PET tracer that binds to intracellular tau depositions. Here, we asses in vivo [F-18]-AV-1451 uptake in several cases of Parkinson syndromes and evaluate the spatial distribution of tau protein accumulations in cortical and subcortical areas by comparison to a cohort of healthy controls.MethodsIn a cohort of 13 patients with Parkinson syndromes (6 PSP, 4 CBS, 2 iPD, 1 cerebellar type MSA), we performed [F-18]-AV-1451 PET. PET data were normalized to MNI space using SPM. We created SUV-Ratio (SUVR) images by intensity normalization to the cerebellum. Preexisting [F-18]-AV-1451 PET-scans of a cohort of 19 healthy controls (HC) were processed equally. For each patient, a 3D dataset was calculated containing the voxelwise Z-transformed deviation of the individual’s SUVR-PET scan from the mean [F-18]-AV-1451 SUVR in the group of healthy controls. ResultsIn comparison to the cohort of healthy controls, all patients with PSP showed increased uptake in the dorsal pallidum and/or midbrain areas. (Figure sections A, B) CBS patients showed a comparatively increased uptake in the basal ganglia and affected cortical areas. (Figure section C). Patients with PD and MSA did not show an increase of uptake in comparison to the cohort of HC.ConclusionCBS and PSP cases clearly showed an increase of [F-18]-AV-1451 uptake in affected areas (midbrain, dorsal pallidum in PSP; cortical regions and basal ganglia in CBS). Voxelwise analysis allowed verification of a pathologically increased tracer uptake in basal ganglia and midbrain above the known unspecific tracer retention in these regions in healthy controls. MSA and iPD - not being associated with a tau pathology – indeed did not show any increase of uptake in comparison to a cohort of healthy controls. These findings indicate that [F-18]-AV-1451-PET has great potential in the diagnostic workup of Parkinson syndromes and the differentiation between iPD, MSA, PSP and CBS. A prospective study is needed to substantiate this finding