bf-227 and Cognition-Disorders

We recently developed a novel PET tracer, (11)C-labeled 2-(2-[2-dimethylaminothiazol-5-yl]ethenyl)-6-(2-[fluoro]ethoxy)benzoxazole ([(11)C]BF-227), and had success with in vivo detection of amyloid plaques in Alzheimer's disease (AD) brains (Kudo et al. in J Nucl Med 8:553-561, 2007). We applied this tracer to subjects with mild cognitive impairment (MCI) and AD in order to elucidate the status of amyloid plaque deposition in MCI and compared the diagnostic performance of BF-227-PET with that of FDG-PET in AD cases. We studied 12 aged normal (AN) subjects, 15 MCIs and 15 ADs with PET using [(11)C]BF-227. PET images were obtained after administration of BF-227 and the regional standardized uptake value (SUV) and the ratio of regional to cerebellar SUV were calculated as an index of BF-227 binding. AD patients showed increased uptake of [(11)C]BF-227 in the neocortical areas and striatum as well as decreased glucose metabolism in temporoparietal, posterior cingulate and medial temporal areas. MCI subjects showed a significant increase in BF-227 uptake in the neocortical areas similar to AD, and the most significant difference of BF-227 retention was observed in the parietal lobe if its retentions for MCI were compared to those for AD and AN. On the other hand, glucose hypometabolism in MCI was confined to cingulate and medial temporal cortices. Neocortical BF-227 uptake negatively correlated with glucose metabolism. Receiver operating characteristic (ROC) analysis indicated higher specificity and sensitivity with BF-227-PET than those with FDG-PET for differential diagnosis between AD and normal control. We conclude that [(11)C]BF-227-PET has a possibility to be a useful technology for early detection of AD pathology and also even in the MCI stage.

Topics: Aged; Alzheimer Disease; Amyloid; Benzoxazoles; Brain; Brain Mapping; Carbon Radioisotopes; Cognition Disorders; Diagnosis, Differential; Female; Fluorodeoxyglucose F18; Glucose; Humans; Male; Plaque, Amyloid; Positron-Emission Tomography; ROC Curve; Sensitivity and Specificity; Thiazoles

Two techniques employed for the early diagnosis of dementia are the imaging of amyloid-beta protein using positron emission tomography (PET) and voxel-based morphometry analysis of MRI (VBM-MRI). The purpose of this study was to evaluate the clinical utility of amyloid PET and VBM-MRI for the early diagnosis and tracking of the severity of Alzheimer's disease (AD). The neuritic plaque burden and gray matter losses were evaluated using [11C]BF-227-PET and VBM-MRI in 12 healthy controls, 13 subjects with mild cognitive impairment (MCI), including 6 who converted to AD and 7 who did not convert, and 15 AD patients. The AD patients and the MCI converters exhibited a neocortical retention of BF-227 and parahippocampal gray matter loss shown by VBM-MRI. The MCI converters were more clearly distinguished from the MCI non-converters in BF-227-PET than VBM-MRI. The combined sample of the MCI converters and AD patients showed a significant correlation of MMSE scores with the global gray matter loss, but not with the BF-227 retention. These findings suggest that amyloid PET using [11C]BF-227 is better suited for the prediction of conversion from MCI to AD, while VBM-MRI appears to be better suited for tracking the severity of dementia.

Topics: Aged; Aged, 80 and over; Alzheimer Disease; Benzoxazoles; Brain; Carbon Radioisotopes; Cognition Disorders; Early Diagnosis; Female; Follow-Up Studies; Humans; Magnetic Resonance Imaging; Male; Neocortex; Nerve Fibers, Unmyelinated; Neuropsychological Tests; Parahippocampal Gyrus; Plaque, Amyloid; Positron-Emission Tomography; Severity of Illness Index; Signal Processing, Computer-Assisted; Thiazoles