Sarker Azmal, Suh Minseok, Choi Yoori, Park Ji Yong, Kwon Seokjun, Kim Hyun, Lee Eunji, Seo Hyeyeon, Lee Yun-Sang, Lee Dong Soo
Department of Nuclear Medicine, College of Medicine, Seoul National University, Seoul, Korea.
Department of Nuclear Medicine, Seoul National University Hospital, Seoul, 03080 Republic of Korea.
Nucl Med Mol Imaging. 2022 Jun;56(3):137-146. doi: 10.1007/s13139-022-00746-6. Epub 2022 Apr 2.
Clearance of brain waste in the cerebrospinal fluid (CSF) through the meningeal lymphatic vessels (mLV) has been evaluated mostly through the fluorescent imaging which has inherent limitations in the context of animal physiology and clinical translatability. The study aimed to establish molecular imaging for the evaluation of mLV clearance function.
Radionuclide imaging after intrathecal (IT) injection was acquired in C57BL/6 mice of 2-9 months. The distribution of [Tc]Tc-diethylenetriamine pentaacetate (DTPA) and [Cu]Cu-human serum albumin (HSA) was comparatively evaluated. Evans Blue and [Cu]Cu-HSA were used to evaluate the distribution of tracer under various speed and volume conditions.
[Tc]Tc-DTPA is not a suitable tracer for evaluation of CSF clearance via mLV as no cervical lymph node uptake was observed while it was cleared from the body. A total volume of 3 to 9 μL at an infusion rate of 300 to 500 nL/min was not sufficient for the tracer to reach the cranial subarachnoid space and clear throughout the mLV. As a result, whole-body positron emission tomography imaging using [Cu]Cu-HSA at 700 nL/min, to deliver 6 μL of injected volume, was set for characterization of the CSF to mLV clearance. Through this protocol, the mean terminal CSF clearance half-life was measured to be 123.6 min (range 117.0-135.0) in normal mice.
We established molecular imaging to evaluate CSF drainage through mLV using [Cu]Cu-HSA. This imaging method is expected to be extended in animal models of dysfunctional meningeal lymphatic clearance and translational research for disease-modifying therapeutic approaches.
The online version contains supplementary material available at 10.1007/s13139-022-00746-6.
通过脑膜淋巴管（mLV）清除脑脊液（CSF）中的脑废物，大多是通过荧光成像进行评估的，而这种成像在动物生理学和临床可转化性方面存在固有限制。本研究旨在建立用于评估mLV清除功能的分子成像。
对2至9个月大的C57BL/6小鼠进行鞘内（IT）注射后进行放射性核素成像。比较评估了[锝]Tc-二乙烯三胺五乙酸（DTPA）和[铜]Cu-人血清白蛋白（HSA）的分布。使用伊文思蓝和[铜]Cu-HSA评估不同速度和体积条件下示踪剂的分布。
[锝]Tc-DTPA不是评估通过mLV清除CSF的合适示踪剂，因为在其从体内清除时未观察到颈部淋巴结摄取。以300至500 nL/分钟的输注速率注入3至9 μL的总体积不足以使示踪剂到达颅蛛网膜下腔并通过mLV清除。因此，设定以700 nL/分钟的速度注射6 μL[铜]Cu-HSA进行全身正电子发射断层扫描成像，以表征CSF至mLV的清除情况。通过该方案，正常小鼠的平均终末CSF清除半衰期测得为123.6分钟（范围117.0 - 135.0）。
我们建立了使用[铜]Cu-HSA评估通过mLV进行CSF引流的分子成像。这种成像方法有望在脑膜淋巴清除功能障碍的动物模型以及疾病修饰治疗方法的转化研究中得到扩展。
在线版本包含可在10.1007/s13139-022-00746-6获取的补充材料。
