Avid Radiopharmaceuticals, Philadelphia, Pennsylvania, USA.
JAMA. 2011 Jan 19;305(3):275-83. doi: 10.1001/jama.2010.2008.
The ability to identify and quantify brain β-amyloid could increase the accuracy of a clinical diagnosis of Alzheimer disease.
To determine if florbetapir F 18 positron emission tomographic (PET) imaging performed during life accurately predicts the presence of β-amyloid in the brain at autopsy.
DESIGN, SETTING, AND PARTICIPANTS: Prospective clinical evaluation conducted February 2009 through March 2010 of florbetapir-PET imaging performed on 35 patients from hospice, long-term care, and community health care facilities near the end of their lives (6 patients to establish the protocol and 29 to validate) compared with immunohistochemistry and silver stain measures of brain β-amyloid after their death used as the reference standard. PET images were also obtained in 74 young individuals (18-50 years) presumed free of brain amyloid to better understand the frequency of a false-positive interpretation of a florbetapir-PET image.
Correlation of florbetapir-PET image interpretation (based on the median of 3 nuclear medicine physicians' ratings) and semiautomated quantification of cortical retention with postmortem β-amyloid burden, neuritic amyloid plaque density, and neuropathological diagnosis of Alzheimer disease in the first 35 participants autopsied (out of 152 individuals enrolled in the PET pathological correlation study).
Florbetapir-PET imaging was performed a mean of 99 days (range, 1-377 days) before death for the 29 individuals in the primary analysis cohort. Fifteen of the 29 individuals (51.7%) met pathological criteria for Alzheimer disease. Both visual interpretation of the florbetapir-PET images and mean quantitative estimates of cortical uptake were correlated with presence and quantity of β-amyloid pathology at autopsy as measured by immunohistochemistry (Bonferroni ρ, 0.78 [95% confidence interval, 0.58-0.89]; P <.001]) and silver stain neuritic plaque score (Bonferroni ρ, 0.71 [95% confidence interval, 0.47-0.86]; P <.001). Florbetapir-PET images and postmortem results rated as positive or negative for β-amyloid agreed in 96% of the 29 individuals in the primary analysis cohort. The florbetapir-PET image was rated as amyloid negative in the 74 younger individuals in the nonautopsy cohort.
Florbetapir-PET imaging was correlated with the presence and density of β-amyloid. These data provide evidence that a molecular imaging procedure can identify β-amyloid pathology in the brains of individuals during life. Additional studies are required to understand the appropriate use of florbetapir-PET imaging in the clinical diagnosis of Alzheimer disease and for the prediction of progression to dementia.
识别和量化大脑β-淀粉样蛋白的能力可以提高阿尔茨海默病临床诊断的准确性。
确定在生命过程中进行的氟[18F]氟替卡培 PET 成像是否能准确预测死后大脑中β-淀粉样蛋白的存在。
设计、地点和参与者：2009 年 2 月至 2010 年 3 月，对临终、长期护理和社区医疗保健机构的 35 名患者进行了前瞻性临床评估，在生命结束时进行了氟[18F]氟替卡培 PET 成像（6 名患者建立方案，29 名患者验证），并与死后使用免疫组织化学和银染测量的脑β-淀粉样蛋白进行比较作为参考标准。还对 74 名年龄在 18-50 岁之间的年轻个体（假定无脑淀粉样蛋白）进行了氟[18F]氟替卡培 PET 成像，以更好地了解氟[18F]氟替卡培 PET 图像假阳性解释的频率。
基于 3 名核医学医师评分中位数的氟[18F]氟替卡培 PET 图像解释与皮质保留的半自动化定量与死后β-淀粉样蛋白负荷、神经原纤维缠结淀粉样斑块密度和阿尔茨海默病的病理诊断的相关性在首次接受尸检的 35 名参与者（152 名参加 PET 病理相关性研究的参与者中）。
29 名主要分析队列中的个体在死亡前平均进行了 99 天（范围为 1-377 天）的氟[18F]氟替卡培 PET 成像。29 名参与者中有 15 名（51.7%）符合阿尔茨海默病的病理标准。氟[18F]氟替卡培 PET 图像的视觉解释以及皮质摄取的平均定量估计均与免疫组织化学（Bonferroni ρ，0.78 [95%置信区间，0.58-0.89]；P <.001）和银染神经原纤维缠结斑块评分（Bonferroni ρ，0.71 [95%置信区间，0.47-0.86]；P <.001）测量的β-淀粉样蛋白病理存在和数量相关。在主要分析队列的 29 名个体中，氟[18F]氟替卡培 PET 图像和死后结果对β-淀粉样蛋白的阳性或阴性评分一致的比例为 96%。在非尸检队列的 74 名年轻个体中，氟[18F]氟替卡培 PET 图像被评为无淀粉样蛋白。
氟[18F]氟替卡培 PET 成像与β-淀粉样蛋白的存在和密度相关。这些数据提供了证据，证明分子成像程序可以在个体的一生中识别大脑中的β-淀粉样蛋白病理。需要进一步研究以了解氟[18F]氟替卡培 PET 成像在阿尔茨海默病的临床诊断和预测痴呆进展中的适当用途。
