Aim: To determine early brain changes in the distribution of an amyloid positron emission tomography (PET) probe, C-11-labeled BF-227 or [C-11] BF-227, in order to accurately predict the progression of mild cognitive impairment (MCI) to Alzheimer's disease (AD). Patients and Methods: Amyloid plaque burden was evaluated using [C-11] BF-227 PET in AD, MCI and aged normal controls. A voxel-based analysis of [C-11] BF-227 PET images was performed to characterize the culprit brain lesion in patients with MCI who were destined to progress to AD, referred to as MCI converters (MCI-C). In addition, binding characteristics of BF-227 to amyloid deposits were examined using postmortem AD brain samples. Results: Voxel-based statistical analyses of the BF-227 PET images clearly demonstrated an abnormal distribution of BF-227 mainly in the posterior association area in MCI-C and patients with AD. BF-227 uptake in the lateral temporal cortex was consistently observed in almost all MCI-C and patients with AD, and it distinguished MCI-C from MCI nonconverters. BF-227 binding strongly correlated with dense amyloid-beta protein plaque density, but not with diffuse plaque density in the frontal cortex. Conclusion: BF-227 uptake in the lateral temporal cortex is a reliable indicator that can be used for predicting prognosis in patients with MCI. Copyright (C) 2010 S. Karger AG, Basel