Department of Regenerative Medicine and Tissue Engineering, National Cerebral and Cardiovascular Center, 6-1 Kishibe-Shimmachi, Suita, Osaka 564-8565, Japan; Department of Neurobiology, Care Sciences & Society, Karolinska Institute, Visionsgatan 4, Solna 171 64, Sweden.
Department of Investigative Radiology, National Cerebral and Cardiovascular Center, 6-1 Kishibe-Shimmachi, Suita, Osaka 564-8565, Japan; Institute of Physics, University of Tsukuba, Ibaraki 305-8571, Japan.
Exp Neurol. 2024 Aug;378:114843. doi: 10.1016/j.expneurol.2024.114843. Epub 2024 May 31.
Poststroke neuroinflammation exacerbates disease progression. [C]PK11195-positron emission tomography (PET) imaging has been used to visualize neuroinflammation; however, its short half-life of 20 min limits its clinical use. [I]CLINDE has a longer half-life (13h); therefore, [I]CLINDE-single-photon emission computed tomography (SPECT) imaging is potentially more practical than [C]PK11195-PET imaging in clinical settings. The objectives of this study were to 1) validate neuroinflammation imaging using [I]CLINDE and 2) investigate the mechanisms underlying stroke in association with neuroinflammation using multimodal techniques, including magnetic resonance imaging (MRI), gas-PET, and histological analysis, in a rat model of ischemic stroke, that is, permanent middle cerebral artery occlusion (pMCAo). At 6 days post-pMCAo, [I]CLINDE-SPECT considerably corresponded to the immunohistochemical images stained with the CD68 antibody (a marker for microglia/microphages), comparable to the level observed in [C]PK11195-PET images. In addition, the [I]CLINDE-SPECT images corresponded well with autoradiography images. Rats with severe infarcts, as defined by MRI, exhibited marked neuroinflammation in the peri-infarct area and less neuroinflammation in the ischemic core, accompanied by a substantial reduction in the cerebral metabolic rate of oxygen (CMRO) in O-gas-PET. Rats with moderate-to-mild infarcts exhibited neuroinflammation in the ischemic core, where CMRO levels were mildly reduced. This study demonstrates that [I]CLINDE-SPECT imaging is suitable for neuroinflammation imaging and that the distribution of neuroinflammation varies depending on the severity of infarction.
中风后的神经炎症会加重疾病进展。[C]PK11195-正电子发射断层扫描（PET）成像已被用于可视化神经炎症；然而，其半衰期仅为 20 分钟，限制了其临床应用。[I]CLINDE 的半衰期较长（13 小时）；因此，[I]CLINDE-单光子发射计算机断层扫描（SPECT）成像在临床环境中比 [C]PK11195-PET 成像更实用。本研究的目的是 1）使用 [I]CLINDE 验证神经炎症成像，2）使用多种技术，包括磁共振成像（MRI）、气体-PET 和组织学分析，研究与神经炎症相关的中风机制，在永久性大脑中动脉闭塞（pMCAo）的大鼠模型中。在 pMCAo 后 6 天，[I]CLINDE-SPECT 与用 CD68 抗体（小胶质细胞/巨噬细胞的标志物）染色的免疫组织化学图像相当对应，与 [C]PK11195-PET 图像观察到的水平相当。此外，[I]CLINDE-SPECT 图像与放射性自显影图像吻合良好。MRI 定义的严重梗死大鼠在梗死周边区表现出明显的神经炎症，在缺血核心区的神经炎症较少，伴有 O-气体-PET 中脑氧代谢率（CMRO）显著降低。中度至轻度梗死大鼠在缺血核心区表现出神经炎症，CMRO 水平略有降低。这项研究表明，[I]CLINDE-SPECT 成像适用于神经炎症成像，神经炎症的分布取决于梗死的严重程度。
