Department of Medical Physics, University of Wisconsin-Madison School of Medicine and Public Health, Madison, Wisconsin
Waisman Laboratory for Brain Imaging and Behavior, University of Wisconsin-Madison School of Medicine and Public Health, Madison, Wisconsin.
J Nucl Med. 2019 Jan;60(1):93-99. doi: 10.2967/jnumed.118.209650. Epub 2018 May 18.
Tau PET imaging has potential for elucidating changes in the deposition of neuropathological tau aggregates that are occurring during the progression of Alzheimer disease (AD). This work investigates in vivo kinetics, quantification strategies, and imaging characteristics of a novel tau PET radioligand F-MK-6240 in humans. Fifty-one individuals ranging from cognitively normal young controls to persons with dementia underwent T1-weighted MRI as well as C-PiB and F-MK-6240 PET imaging. PET data were coregistered to the MRI, and time-activity curves were extracted from regions of interest to assess F-MK-6240 kinetics. The pons and inferior cerebellum were investigated as potential reference regions. Reference tissue methods (Logan graphical analysis [LGA] and multilinear reference tissue method [MRTM2]) were investigated for quantification of F-MK-6240 distribution volume ratios (DVRs) in a subset of 19 participants. Stability of DVR methods was evaluated using truncated scan durations. SUV ratio (SUVR) estimates were compared with DVR estimates to determine the optimal timing window for SUVR analysis. Parametric SUVR images were used to identify regions of potential off-target binding and to compare binding patterns with neurofibrillary tau staging established in neuropathology literature. SUVs in the pons and the inferior cerebellum indicated consistent clearance across all 51 subjects. LGA and MRTM2 DVR estimates were similar, with LGA slightly underestimating DVR compared with MRTM2. DVR estimates remained stable when truncating the scan duration to 60 min. SUVR determined 70-90 min after injection of F-MK-6240 indicated linearity near unity when compared with DVR estimates and minimized potential spill-in from uptake outside the brain. F-MK-6240 binding patterns in target regions were consistent with neuropathological neurofibrillary tau staging. Off-target binding regions included the ethmoid sinus, clivus, meninges, substantia nigra, but not the basal ganglia or choroid plexus. F-MK-6240 is a promising PET radioligand for in vivo imaging of neurofibrillary tau aggregates in AD with minimal off-target binding in the human brain.
tau PET 成像有可能阐明在阿尔茨海默病（AD）进展过程中神经病理 tau 聚集体沉积的变化。本研究探讨了新型 tau PET 放射性配体 F-MK-6240 在人体内的体内动力学、定量策略和成像特征。 51 名个体从认知正常的年轻对照者到痴呆患者，均接受了 T1 加权 MRI 以及 C-PiB 和 F-MK-6240 PET 成像。将 PET 数据与 MRI 配准，并从感兴趣区域提取时间-活性曲线，以评估 F-MK-6240 的动力学。桥脑和小脑蚓部被作为潜在的参照区域进行了研究。在 19 名参与者的亚组中，使用 Logan 图形分析（LGA）和多线性参照组织方法（MRTM2）研究了参照组织方法（LGA）和多线性参照组织方法（MRTM2）来定量 F-MK-6240 分布容积比（DVR）。使用截断扫描时间来评估 DVR 方法的稳定性。比较了 SUV 比（SUVr）估计值与 DVR 估计值，以确定 SUVr 分析的最佳时间窗。使用参数化 SUVr 图像来识别潜在的脱靶结合区域，并比较与神经纤维缠结 tau 分期的结合模式，该分期建立在神经病理学文献中。 在所有 51 名受试者中，桥脑和小脑蚓部的 SUV 均显示出一致的清除率。LGA 和 MRTM2 的 DVR 估计值相似，LGA 与 MRTM2 相比略低估了 DVR。当扫描时间截断至 60 分钟时，DVR 估计值保持稳定。与 DVR 估计值相比，注射 F-MK-6240 后 70-90 分钟的 SUVr 呈近单位线性，最大限度地减少了来自脑外摄取的潜在干扰。目标区域内的 F-MK-6240 结合模式与神经病理学神经纤维缠结 tau 分期一致。脱靶结合区域包括筛窦、斜坡、脑膜、黑质，但不包括基底节或脉络丛。F-MK-6240 是一种很有前途的用于 AD 中神经纤维缠结 tau 聚集体的体内成像的 PET 放射性配体，在人脑内具有最小的脱靶结合。
