National Hospital for Geriatric Medicine, National Center for Geriatrics and Gerontology, Obu, Japan; Department of Clinical and Experimental Neuroimaging, Center for Development of Advanced Medicine for Dementia, National Center for Geriatrics and Gerontology, Obu, Japan.
National Hospital for Geriatric Medicine, National Center for Geriatrics and Gerontology, Obu, Japan; Department of Clinical and Experimental Neuroimaging, Center for Development of Advanced Medicine for Dementia, National Center for Geriatrics and Gerontology, Obu, Japan.
Nucl Med Biol. 2022 May-Jun;108-109:76-84. doi: 10.1016/j.nucmedbio.2022.02.005. Epub 2022 Mar 12.
C-DPA-713 is a positron emission tomography (PET) radiotracer developed for imaging the expression of the translocator protein (TSPO) in glial cells, which is considered to be a marker of the neuroinflammatory burden. This study investigated the pharmacokinetic profile of C-DPA-713 and evaluated kinetic modeling and non-invasive TSPO quantification using dynamic PET imaging data in the Alzheimer's disease (AD) and cognitive normal (CN) participants.
Eleven patients with AD and 6 CN participants were examined using dynamic C-DPA-713 PET imaging for 60 min with arterial blood sampling. Time-activity curves were calculated from the cerebellum and three composite regions of interest (ROIs), according to the anatomical definitions of Braak's stages 1 to 3, stage 4, stage 5, and stage 6 that correspond to the pathological stages of tangle deposition. The total distribution volume (V) was evaluated using compartmental modeling and graphical analysis. Reference region-based methods were implemented using an optimal area that was assumed to be void of the radiotracer target as reference tissue.
The concentration of radioactivity in plasma demonstrated rapid clearance. C-DPA-713 peaked rapidly in the gray matter. Compartmental modeling resulted in a good fit, and the one-tissue model with estimated blood volume correction (1Tv) showed the best performance. The estimated V obtained from the graphical plasma methods was highly correlated with that obtained from 1Tv. Reference region-based analysis was conducted using the Braak 6 area as the reference region, and the estimated non-displaceable binding potential was highly correlated with that obtained from 1Tv.
C-DPA-713 possesses properties suitable for TSPO quantification with PET imaging. The Braak 6 area was shown to be a useful reference region in the patients with AD and the CN participants, and non-invasive reference tissue models using the Braak 6 area as a reference region can be employed for TSPO quantification with C-DPA-713-PET imaging as an alternative to the invasive compartmental model.
C-DPA-713 是一种正电子发射断层扫描（PET）示踪剂，用于对神经胶质细胞中转位蛋白（TSPO）的表达进行成像，该蛋白被认为是神经炎症负担的标志物。本研究调查了 C-DPA-713 的药代动力学特征，并使用阿尔茨海默病（AD）和认知正常（CN）参与者的动态 PET 成像数据评估了动力学建模和非侵入性 TSPO 定量。
11 名 AD 患者和 6 名 CN 参与者接受了 60 分钟的 C-DPA-713 动态 PET 成像检查，并进行了动脉采血。根据 Braak 阶段 1 至 3、阶段 4、阶段 5 和阶段 6 的解剖定义，从小脑和三个复合感兴趣区（ROI）计算时间-活性曲线，这些阶段分别对应于缠结沉积的病理阶段。使用房室模型和图形分析评估总分布容积（V）。使用假定无示踪剂靶标作为参考组织的最佳区域实施基于参考区的方法。
血浆中放射性物质的浓度迅速清除。C-DPA-713 在灰质中迅速达到峰值。房室模型拟合良好，估计血容量校正的单组织模型（1Tv）表现最佳。图形血浆方法估计的 V 与 1Tv 获得的 V 高度相关。使用 Braak 6 区作为参考区进行基于参考区的分析，估计的不可置换结合势与 1Tv 获得的结合势高度相关。
C-DPA-713 具有适合使用 PET 成像进行 TSPO 定量的特性。Braak 6 区被证明是 AD 患者和 CN 参与者的有用参考区，并且可以使用 Braak 6 区作为参考区的非侵入性参考组织模型来替代侵入性房室模型，用于 C-DPA-713-PET 成像的 TSPO 定量。
