Department of Pathology, The University of Melbourne, Victoria 3010, Australia.
Nucl Med Biol. 2012 Oct;39(7):1042-8. doi: 10.1016/j.nucmedbio.2012.03.001. Epub 2012 Apr 11.
Amyloid-β (Aβ) plaques are a major pathological hallmark of Alzheimer's disease (AD). The noninvasive detection of Aβ plaques may increase the accuracy of clinical diagnosis as well as monitor therapeutic interventions. While [(11)C]-PiB is the most widely used Aβ positron emission tomography (PET) radiotracer, due to the short half-life of (11)C (20 min), its application is limited to centers with an on-site cyclotron and (11)C radiochemistry expertise. Therefore, novel [(18)F] (half-life 110 min)-labeled Aβ PET tracers have been developed. We have demonstrated that [(18)F]-florbetaben-PET can differentiate individuals diagnosed with AD from healthy elderly, Parkinson's disease and frontotemporal lobe dementia (FTLD-tau) patients. While [(18)F]-florbetaben-PET retention matched the reported postmortem distribution of Aβ plaques, the nature of [(18)F]-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 Aβ plaques in postmortem tissue specimens containing mixed pathological hallmarks (i.e., tau and α-synuclein aggregates).
Human AD, FTLD-tau and dementia with Lewy bodies (DLB) brain sections were analyzed by [(18)F]-florbetaben autoradiography and [(3)H]-florbetaben high-resolution emulsion autoradiography and [(19)F]-florbetaben fluorescence microscopy.
Both autoradiographical analyses demonstrated that Florbetaben exclusively bound Aβ plaques in AD brain sections at low nanomolar concentrations. Furthermore, at concentrations thousand-folds higher than those during a PET scan, [(19)F]-florbetaben did not bind to α-synuclein or tau aggregates in DLB and FTLD-tau brain sections, respectively. Detection of [(19)F]-florbetaben staining by fluorescence microscopy in several AD brain regions demonstrated that Florbetaben identified Aβ plaques in all brain regions examined.
This study provides further evidence that [(18)F]-florbetaben-PET is a highly selective radiotracer to assess Aβ plaque deposition in the brain.
淀粉样蛋白-β（Aβ）斑块是阿尔茨海默病（AD）的主要病理标志物。Aβ斑块的非侵入性检测可以提高临床诊断的准确性，并监测治疗干预效果。虽然[(11)C]-PiB 是最广泛使用的 Aβ 正电子发射断层扫描（PET）放射性示踪剂，但由于(11)C 的半衰期较短（20 分钟），其应用仅限于拥有现场回旋加速器和(11)C 放射化学专业知识的中心。因此，已经开发了新型[(18)F]（半衰期 110 分钟）-标记的 Aβ PET 示踪剂。我们已经证明，[(18)F]-florbetaben-PET 可以区分被诊断为 AD 的个体与健康老年人、帕金森病和额颞叶痴呆（FTLD-tau）患者。虽然[(18)F]-florbetaben-PET 的保留与 Aβ斑块的报告死后分布相匹配，但[(18)F]-florbetaben 与其他包含错误折叠蛋白的病理病变结合的性质需要进一步评估。本研究的目的是确定 Florbetaben 是否选择性地结合包含混合病理标志物（即 tau 和α-突触核蛋白聚集体）的死后组织标本中的 Aβ斑块。
通过[(18)F]-florbetaben 放射自显影和[(3)H]-florbetaben 高分辨率乳胶放射自显影以及[(19)F]-florbetaben 荧光显微镜分析人类 AD、FTLD-tau 和路易体痴呆（DLB）脑切片。
两种放射自显影分析均表明，在低纳摩尔浓度下，Florbetaben 仅结合 AD 脑切片中的 Aβ斑块。此外，在 PET 扫描期间浓度千倍以上时，[(19)F]-florbetaben 分别不会与 DLB 和 FTLD-tau 脑切片中的α-突触核蛋白或 tau 聚集体结合。荧光显微镜检测 AD 大脑多个区域的[(19)F]-florbetaben 染色表明，Florbetaben 在所有检查的大脑区域中均识别出 Aβ斑块。
本研究进一步证明，[(18)F]-florbetaben-PET 是一种高度选择性的放射性示踪剂，可用于评估大脑中 Aβ斑块的沉积。
