Presentation Clinical significance of tau accumulation assessed by [11C]PBB3 PET in diverse tauopathies

島田, 斉  ,  須原, 哲也  ,  篠遠, 仁  ,  平野, 成樹  ,  山田, 真希子  ,  木村, 泰之  ,  佐原, 成彦  ,  張, 明栄  ,  伊藤, 浩  ,  樋口, 真人  ,  桑原, 聡

Background and aims:Tau neurofibrillary changes is considered to be a promising target for imaging and therapy in Alzheimer’s disease (AD) and non-AD tauopathies such as progressive supuranuclear palsy (PSP), corticobasal syndrome (CBS) and frontotemporal dementia (FTD). In addition, some neuropathologists regard tau tangles in the brain as an inevitable consequence of aging even in cognitively healthy subjects. [11C]PBB3 is a novel tau imaging PET ligand, which could visualize the tau deposition in AD and non-AD tauopathies. The aim of this study is to investigate the diagnostic utility and the clinical significance of tau PET imaging with [11C]PBB3.Methods:Participants were 21 AD patients, 16 mild cognitive impairments (MCI) patients, ten PSP patients, nine CBS patients, six FTD patients, and 34 cognitively healthy controls (HC) consisted of 24 age-matched elderly control and 10 young HCs. We performed PET scans with [11C]PBB3 and [11C]Pib for imaging of tau and Aβ lesions, respectively, and metabolic radiotracer [18F]FDG, along with MRI, neurological examination and psychological batteries. Voxel-based calculation of standardized uptake value ratio (SUVR) to the cerebellum was employed for quantification. We carried out a voxel-by-voxel correlation analysis between [11C]PBB3 SUVR and age for Aβ-negative HC group, in order to explore brain regions exhibiting an age-related increase. We additionally performed voxel-based correlation analyses between SUVRs for each radiotracer and neuropsychological test scores.Results:All AD patients, ten of 16 MCI patients, one of nine CBS patient, one FTD patient, and three of 24 old HCs were Aβ-positive. Some Aβ-negative old HCs showed PBB3 uptake around medial temporal cortex. Furthermore, [11C]PBB3 retention was positively correlated with age in a few areas including the bilateral medial to inferior temporal cortices in 31 Aβ-negative HCs. Distribution patterns of [11C] PBB3 accumulation were different among each patient group, and [11C]PBB3 uptake were observed in lesions associated with neurological symptoms in each disease. In AD spectrum, brain regions with higher [11C]PBB3 binding expanded as a function of cognitive decline from Aβ-positive MCI to AD, whereas distribution of increased [11C]Pib binding was unaltered. Mean cortical SUVR of [11C]PBB3 was increased in Aβ-positive MCI and AD groups by 15% and 30%, respectively, relative to HCs. General clinical dementia scale was correlated with increased [11C]PBB3 SUVR in extensive brain regions, and memory and frontal scores were associated with [11C]PBB3 SUVR in reported functional regions in Aβ-positive MCI and AD groups. Spatial and temporal distribution of impaired [18F]FDG uptake appeared to follow the increase of [11C]PBB3 SUVR.Conclusions:Tau imaging with [11C]PBB3 and PET is useful for pursuing pathological advancement from normal aging to MCI and from MCI to AD, and provides an objective index of the disease severity and molecular basis of neurologic and neuropsychological manifestations. Furthermore, Tau PET imaging using [11C]PBB3 could help a differential diagnosis among HCs and a variety of AD and non-AD tauopathies.
2015 World Molecular Imaging Congress

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