In vitro characterization of [¹⁸F]-florbetaben, an A¦Â imaging radiotracer

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• 作者：Michelle T. Fodero-Tavoletti ; Damian Brockschnieder ; Victor L. Villemagne ; Lucas Martin ; Andrea R. Connor ; Andrea Thiele ; Mathias Berndt ; Catriona A. McLean ; Sabine Krause ; Christopher C. Rowe ; Colin L. Masters ; Ludger Dinkelborg ; Thomas Dyrks ; Roberto Cappai
• 关键词：A¦Â ; Imaging ; Alzheimer's disease ; Dementia ; PET
• 刊名：Nuclear Medicine and Biology
• 出版年：2012
• 出版时间：October, 2012
• 年：2012
• 卷：39
• 期：7
• 页码：1042-1048
• 全文大小：1489 K

文摘

Purpose

Amyloid-¦Â (A¦Â) plaques are a major pathological hallmark of Alzheimer's disease (AD). The noninvasive detection of A¦Â plaques may increase the accuracy of clinical diagnosis as well as monitor therapeutic interventions. While [¹¹C]-PiB is the most widely used A¦Â positron emission tomography (PET) radiotracer, due to the short half-life of ¹¹C (20?min), its application is limited to centers with an on-site cyclotron and ¹¹C radiochemistry expertise. Therefore, novel [¹⁸F] (half-life 110?min)-labeled A¦Â PET tracers have been developed. We have demonstrated that [¹⁸F]-florbetaben-PET can differentiate individuals diagnosed with AD from healthy elderly, Parkinson's disease and frontotemporal lobe dementia (FTLD-tau) patients. While [¹⁸F]-florbetaben-PET retention matched the reported postmortem distribution of A¦Â plaques, the nature of [¹⁸F]-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¦Â plaques in postmortem tissue specimens containing mixed pathological hallmarks (i.e., tau and ¦Á-synuclein aggregates).

Method

Human AD, FTLD-tau and dementia with Lewy bodies (DLB) brain sections were analyzed by [¹⁸F]-florbetaben autoradiography and [³H]-florbetaben high-resolution emulsion autoradiography and [¹⁹F]-florbetaben fluorescence microscopy.

Results

Both autoradiographical analyses demonstrated that Florbetaben exclusively bound A¦Â plaques in AD brain sections at low nanomolar concentrations. Furthermore, at concentrations thousand-folds higher than those during a PET scan, [¹⁹F]-florbetaben did not bind to ¦Á-synuclein or tau aggregates in DLB and FTLD-tau brain sections, respectively. Detection of [¹⁹F]-florbetaben staining by fluorescence microscopy in several AD brain regions demonstrated that Florbetaben identified A¦Â plaques in all brain regions examined.

Conclusion

This study provides further evidence that [¹⁸F]-florbetaben-PET is a highly selective radiotracer to assess A¦Â plaque deposition in the brain.