Gordon Center for Medical Imaging, Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts;
Gordon Center for Medical Imaging, Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts.
J Nucl Med. 2023 Jun;64(6):968-975. doi: 10.2967/jnumed.122.265072. Epub 2023 Mar 30.
6-(fluoro-F)-3-(1H-pyrrolo[2,3-c]pyridin-1-yl)isoquinolin-5-amine ([F]MK6240) has high affinity and selectivity for hyperphosphorylated tau and readily crosses the blood-brain barrier. This study investigated whether the early phase of [F]MK6240 can be used to provide a surrogate index of cerebral perfusion. Forty-nine subjects who were cognitively normal (CN), had mild cognitive impairment (MCI), or had Alzheimer's disease (AD) underwent paired dynamic [F]MK6240 and [C]Pittsburgh compound B (PiB) PET, as well as structural MRI to obtain anatomic information. Arterial blood samples were collected in a subset of 24 subjects for [F]MK6240 scans to derive metabolite-corrected arterial input functions. Regional time-activity curves were extracted using atlases available in the Montreal Neurologic Institute template space and using FreeSurfer. The early phase of brain time-activity curves was analyzed using a 1-tissue-compartment model to obtain a robust estimate of the rate of transfer from plasma to brain tissue, (mL⋅cm⋅min), and the simplified reference tissue model 2 was investigated for noninvasive estimation of the relative delivery rate, (unitless). A head-to-head comparison with derived from [C]PiB scans was performed. Grouped differences in were evaluated among CN, MCI, and AD subjects. Regional values suggested a relatively high extraction fraction. estimated noninvasively from simplified reference tissue model 2 agreed well with calculated indirectly from the blood-based compartment modeling ( = 0.99; mean difference, 0.024 ± 0.027), suggesting that robust estimates were obtained. measurements obtained with [F]MK6240 correlated strongly and overall agreed well with those obtained from [C]PiB ( = 0.93; mean difference, -0.001 ± 0.068). Statistically significant differences were observed in regional measurements among CN, MCI, and AD subjects, notably in the temporal and parietal cortices. Our results provide evidence that the early phase of [F]MK6240 images may be used to derive a useful index of cerebral perfusion. The early and late phases of a [F]MK6240 dynamic acquisition may thus offer complementary information about the pathophysiologic mechanisms of the disease.
6-(氟代-F)-3-(1H-吡咯并[2,3-c]吡啶-1-基)异喹啉-5-胺([F]MK6240)对过度磷酸化 tau 具有高亲和力和选择性，并且容易穿过血脑屏障。本研究旨在探讨[F]MK6240 的早期阶段是否可用于提供脑灌注的替代指标。49 名认知正常（CN）、轻度认知障碍（MCI）或阿尔茨海默病（AD）患者接受了配对的[F]MK6240 和[C]匹兹堡化合物 B（PiB）PET 动态扫描以及结构 MRI，以获取解剖学信息。在 24 名受试者的亚组中采集了动脉血样，用于[F]MK6240 扫描以获得代谢校正的动脉输入函数。使用 Montreal Neurologic Institute 模板空间中的图谱和 FreeSurfer 提取了区域时间-活性曲线。使用 1 组织室模型分析脑时间-活性曲线的早期阶段，以获得从血浆到脑组织的转移率的稳健估计值（mL·cm·min），并研究简化参考组织模型 2 以无创估计相对输送率（无量纲）。与[C]PiB 扫描得出的进行了直接比较。评估了 CN、MCI 和 AD 受试者之间的分组差异。区域值提示相对较高的提取分数。简化参考组织模型 2 无创估计的与间接从基于血液的房室建模计算的相符（=0.99；平均差异，0.024±0.027），这表明获得了稳健的估计值。用[F]MK6240 获得的测量值与用[C]PiB 获得的测量值强烈相关且总体上一致（=0.93；平均差异，-0.001±0.068）。在 CN、MCI 和 AD 受试者中，观察到区域测量值存在统计学显著差异，尤其是在颞叶和顶叶皮层。我们的结果提供了证据，表明[F]MK6240 图像的早期阶段可用于得出有用的脑灌注指数。因此，[F]MK6240 动态采集的早期和晚期阶段可能提供有关疾病病理生理机制的互补信息。
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