Nuclear Medicine and Molecular Imaging, University of Groningen, University Medical Center Groningen, Hanzeplein 1, Groningen, The Netherlands.
Department of Biomedical Sciences of Cells and Systems, University of Groningen, University Medical Center Groningen, Hanzeplein 1, 9713GZ, Groningen, The Netherlands.
Eur J Nucl Med Mol Imaging. 2022 Aug;49(10):3492-3507. doi: 10.1007/s00259-022-05770-4. Epub 2022 Apr 2.
Multiple sclerosis (MS) is a disease characterized by inflammatory demyelinated lesions. New treatment strategies are being developed to stimulate myelin repair. Quantitative myelin imaging could facilitate these developments. This first-in-man study aimed to evaluate [C]MeDAS as a PET tracer for myelin imaging in humans.
Six healthy controls and 11 MS patients underwent MRI and dynamic [C]MeDAS PET scanning with arterial sampling. Lesion detection and classification were performed on MRI. [C]MeDAS time-activity curves of brain regions and MS lesions were fitted with various compartment models for the identification of the best model to describe [C]MeDAS kinetics. Several simplified methods were compared to the optimal compartment model.
Visual analysis of the fits of [C]MeDAS time-activity curves showed no preference for irreversible (2T3k) or reversible (2T4k) two-tissue compartment model. Both volume of distribution and binding potential estimates showed a high degree of variability. As this was not the case for 2T3k-derived net influx rate (K), the 2T3k model was selected as the model of choice. Simplified methods, such as SUV and MLAIR2 correlated well with 2T3k-derived K, but SUV showed subject-dependent bias when compared to 2T3k. Both the 2T3k model and the simplified methods were able to differentiate not only between gray and white matter, but also between lesions with different myelin densities.
[C]MeDAS PET can be used for quantification of myelin density in MS patients and is able to distinguish differences in myelin density within MS lesions. The 2T3k model is the optimal compartment model and MLAIR2 is the best simplified method for quantification.
NL7262. Registered 18 September 2018.
多发性硬化症（MS）是一种以炎症性脱髓鞘病变为特征的疾病。新的治疗策略正在被开发出来以刺激髓鞘修复。定量髓鞘成像可以促进这些进展。这项首次人体研究旨在评估 [C]MeDAS 作为人类髓鞘成像的 PET 示踪剂。
6 名健康对照者和 11 名 MS 患者接受 MRI 和动态 [C]MeDAS PET 扫描，并进行动脉采样。对 MRI 进行病变检测和分类。对脑区和 MS 病变的 [C]MeDAS 时间-活性曲线进行拟合，采用各种隔室模型来确定描述 [C]MeDAS 动力学的最佳模型。将几种简化方法与最优隔室模型进行比较。
[C]MeDAS 时间-活性曲线拟合的直观分析表明，不可逆（2T3k）或可逆（2T4k）双组织隔室模型均无偏好。分布容积和结合势的估计值都显示出高度的可变性。由于这不是 2T3k 衍生的净流入率（K）的情况，因此选择 2T3k 模型作为首选模型。简化方法，如 SUV 和 MLAIR2 与 2T3k 衍生的 K 相关性良好，但与 2T3k 相比，SUV 显示出与个体相关的偏差。2T3k 模型和简化方法不仅能够区分灰质和白质，还能够区分 MS 病变内的髓鞘密度差异。
[C]MeDAS PET 可用于 MS 患者髓鞘密度的定量，并能够区分 MS 病变内髓鞘密度的差异。2T3k 模型是最佳隔室模型，MLAIR2 是最佳简化方法。
NL7262。于 2018 年 9 月 18 日注册。
Zotero 插件
