Department of Nuclear Medicine, University Hospital, Ludwig-Maximilians University Munich, Marchioninistr. 15, 81377, Munich, Germany.
Institute of Clinical Neuroimmunology, University Hospital, LMU Munich, Munich, Germany.
Eur J Nucl Med Mol Imaging. 2018 Jul;45(8):1423-1431. doi: 10.1007/s00259-018-3974-7. Epub 2018 Mar 9.
Expression of the translocator protein (TSPO) is upregulated in activated macrophages/microglia and is considered to be a marker of neuroinflammation. We investigated the novel TSPO ligand [F]GE-180 in patients with relapsing-remitting multiple sclerosis (RRMS) to determine the feasibility of [F]GE-180 PET imaging in RRMS patients and to assess its ability to detect active inflammatory lesions in comparison with the current gold standard, contrast-enhanced magnetic resonance imaging (MRI).
Nineteen RRMS patients were prospectively included in this study. All patients underwent TSPO genotyping and were classified as high-affinity, medium-affinity or low-affinity binders (HAB/MAB/LAB). PET scans were performed after administration of 189 ± 12 MBq [F]GE-180, and 60-90 min summation images were used for visual analysis and assessment of standardized uptake values (SUV). The frontal nonaffected cortex served as a pseudoreference region (PRR) for evaluation of SUV ratios (SUVR). PET data were correlated with MRI signal abnormalities, i.e. T2 hyperintensity or contrast enhancement (CE). When available, previous MRI data were used to follow the temporal evolution of individual lesions.
Focal lesions were identified as hot spots by visual inspection. Such lesions were detected in 17 of the 19 patients and overall 89 [F]GE-180-positive lesions were found. TSPO genotyping revealed 11 patients with HAB status, 5 with MAB status and 3 with LAB status. There were no associations between underlying binding status (HAB, MAB and LAB) and the signal intensity in either lesions (SUVR 1.87 ± 0.43, 1.95 ± 0.48 and 1.86 ± 0.80, respectively; p = 0.280) or the PRR (SUV 0.36 ± 0.03, 0.40 ± 0.06 and 0.37 ± 0.03, respectively; p = 0.990). Of the 89 [F]GE-180-positive lesions, 70 showed CE on MRI, while the remainder presented as T2 lesions without CE. SUVR were significantly higher in lesions with CE than in those without (2.00 ± 0.53 vs. 1.60 ± 0.15; p = 0.001). Notably, of 19 [F]GE-180-positive lesions without CE, 8 previously showed CE, indicating that [F]GE-180 imaging may be able to detect lesional activity that is sustained beyond the blood-brain barrier breakdown.
[F]GE-180 PET can detect areas of focal macrophage/microglia activation in patients with RRMS in lesions with and without CE on MRI. Therefore, [F]GE-180 PET imaging is a sensitive and quantitative approach to the detection of active MS lesions. It may provide information beyond contrast-enhanced MRI and is readily applicable to all patients. [F]GE-180 PET imaging is therefore a promising new tool for the assessment of focal inflammatory activity in MS.
转位蛋白（TSPO）的表达在激活的巨噬细胞/小胶质细胞中上调，被认为是神经炎症的标志物。我们研究了新型 TSPO 配体 [F]GE-180 在复发性缓解型多发性硬化症（RRMS）患者中的应用，以确定 [F]GE-180 PET 成像在 RRMS 患者中的可行性，并评估其与当前金标准（对比增强磁共振成像（MRI））相比检测活跃炎症病变的能力。
19 例 RRMS 患者前瞻性纳入本研究。所有患者均进行 TSPO 基因分型，并分为高亲和力、中亲和力或低亲和力结合者（HAB/MAB/LAB）。给予 189±12MBq [F]GE-180 后进行 PET 扫描，使用 60-90 分钟总和图像进行视觉分析和标准化摄取值（SUV）评估。额叶非受累皮质作为伪参考区（PRR）用于评估 SUV 比值（SUVR）。将 PET 数据与 MRI 信号异常（即 T2 高信号或对比增强（CE））相关联。当有条件时，使用以前的 MRI 数据来跟踪个体病变的时间演变。
通过视觉检查确定焦点病变为热点。19 例患者中有 17 例发现了这样的病变，共发现了 89 个 [F]GE-180 阳性病变。TSPO 基因分型显示 11 例患者为 HAB 状态，5 例为 MAB 状态，3 例为 LAB 状态。在病变（SUVR 1.87±0.43、1.95±0.48 和 1.86±0.80，分别；p=0.280）或 PRR（SUV 0.36±0.03、0.40±0.06 和 0.37±0.03，分别；p=0.990）中，基础结合状态（HAB、MAB 和 LAB）之间没有关联。在 89 个 [F]GE-180 阳性病变中，70 个在 MRI 上显示 CE，而其余的则表现为无 CE 的 T2 病变。CE 病变的 SUVR 明显高于无 CE 病变（2.00±0.53 比 1.60±0.15；p=0.001）。值得注意的是，在 19 个无 CE 的 [F]GE-180 阳性病变中，有 8 个以前显示过 CE，表明 [F]GE-180 成像可能能够检测到持续存在于血脑屏障破坏之外的病变活性。
[F]GE-180 PET 可在 MRI 上有或无 CE 的 RRMS 患者中检测到局灶性巨噬细胞/小胶质细胞激活区域。因此，[F]GE-180 PET 成像是一种敏感和定量的方法，可用于检测活跃的 MS 病变。它可能提供对比增强 MRI 之外的信息，并且易于应用于所有患者。[F]GE-180 PET 成像因此成为评估 MS 中局灶性炎症活动的有前途的新工具。
