Test–retest characteristic of [18F]MK-6240 quantitative outcomes in cognitively normal adults and subjects with Alzheimer’s disease

C. Salinas, Talakad G. Lohith, Ajay Purohit, A. Struyk, C. Sur, I. Bennacef, J. Beaver, L. Martarello
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引用次数: 18

Abstract

[18F]MK-6240 is a selective, high-affinity PET radiotracer for imaging neurofibrillary tangles (NFT) in Alzheimer’s disease (AD). Herein, we report test–retest (T–RT) reproducibility of [18F]MK-6240 in AD and healthy volunteers (HV). Twelve subjects with AD and three cognitively normal HV were enrolled in the study and dynamically scanned for 150 min with [18F]MK-6240 under a T–RT protocol. Two radioactivity doses were investigated: 165 ± 3 MBq (n = 6) and 300 ± 40 MBq (n = 9). Serial arterial blood samples were taken for each scan to obtain metabolite-corrected input functions. Following intravenous administration of [18F]MK-6240, the tracer rapidly partitioned into the brain and its heterogenous distribution pattern was consistent with known NFT pathology in AD. In contrast, uptake in HV was low and uniform across the brain parenchyma. Across all subjects, average T–RT variabilities in NFT-rich regions were ∼21%, ∼14% and ∼6% for various quantitative metrics: total distribution volume (VT), binding potential (BPND), and standardized uptake ratio (SUVR90–120), respectively. No significant differences in SUVR T–RT variability were observed between the high and low injected radioactivity groups (5.6% and 6.1%, respectively). This work suggests [18F]MK-6240 has adequate SUVR T–RT characteristics supporting the use of this outcome in future studies.
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认知正常成人和阿尔茨海默病患者[18F]MK-6240定量结果的重测特征
[18F]MK-6240是一种选择性的、高亲和力的PET放射性示踪剂,用于成像阿尔茨海默病(AD)的神经原纤维缠结(NFT)。在此,我们报告了[18F]MK-6240在AD和健康志愿者(HV)中的重测(T-RT)可重复性。12名AD患者和3名认知正常的HV患者被纳入研究,并在T-RT协议下用[18F]MK-6240动态扫描150分钟。研究了两种放射性剂量:165±3 MBq (n = 6)和300±40 MBq (n = 9)。每次扫描都要采集一系列动脉血液样本,以获得代谢物校正的输入函数。静脉注射[18F]MK-6240后,示踪剂迅速进入大脑,其异质性分布模式与已知的AD NFT病理一致。相比之下,HV在整个脑实质中的摄取低且均匀。在所有受试者中,nft丰富区域的平均T-RT变异率在各种定量指标上分别为~ 21%、~ 14%和~ 6%:总分布体积(VT)、结合电位(BPND)和标准化摄取比(SUVR90-120)。高、低注射放射性组间SUVR T-RT变异性无显著差异(分别为5.6%和6.1%)。这项研究表明[18F]MK-6240具有足够的SUVR T-RT特征,支持在未来的研究中使用这一结果。
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