In vitro characterization of [18F]-florbetaben, an Aβ imaging radiotracer

Purpose: Amyloid-beta (A beta) plagues are a major pathological hallmark of Alzheimer's disease (AD). The noninvasive detection of A beta plagues may increase the accuracy of clinical diagnosis as well as monitor therapeutic interventions. While [C-11]-PiB is the most widely used A beta positron emission tomography (PET) radiotracer, due to the short half-life of C-11 (20 min), its application is limited to centers with an on-site cyclotron and C-11 radiochemistry expertise. Therefore, novel [F-18] (half-life 110 min)-labeled A beta PET tracers have been developed. We have demonstrated that [F-18]-florbetaben-PET can differentiate individuals diagnosed with AD from healthy elderly, Parkinson's disease and frontotemporal lobe dementia (FTLD-tau) patients. While [F-18]-florbetaben-PET retention matched the reported postmortem distribution of A beta plagues, the nature of [F-18]-florbetaben binding to other pathological lesions comprising misfolded proteins needs further assessment. The objective of this study was to determine whether Florbetaben selectively binds to A beta plagues in postmortem tissue specimens containing mixed pathological hallmarks (i.e., tau and alpha-synuclein aggregates). Method: Human AD, FTLD-tau and dementia with Lewy bodies (DLB) brain sections were analyzed by [F-18]-florbetaben autoradiography and [H-3]-florbetaben high-resolution emulsion autoradiography and [F-19]-florbetaben fluorescence microscopy. Results: Both autoradiographical analyses demonstrated that Florbetaben exclusively bound A beta plagues in AD brain sections at low nanomolar concentrations. Furthermore, at concentrations thousand-folds higher than those during a PET scan, [F-19]-florbetaben did not bind to alpha-synuclein or tau aggregates in DLB and FTLD-tau brain sections, respectively. Detection of [F-19]-florbetaben staining by fluorescence microscopy in several AD brain regions demonstrated that Florbetaben identified A beta plaques in all brain regions examined. Conclusion: This study provides further evidence that [F-18]-florbetaben-PET is a highly selective radiotracer to assess A beta plague deposition in the brain. (c) 2012 Elsevier Inc. All rights reserved.