Molecular imaging of mesothelioma by detection of manganese-superoxide dismutase activity using manganese-enhanced magnetic resonance imaging
Molecular imaging of mesothelioma by detection of manganese-superoxide dismutase activity using manganese-enhanced magnetic resonance imaging
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DOI：
10.1002/ijc.25547
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发表时间：
2011-05-01
影响因子：
6.4
通讯作者：
Saga, Tsuneo
中科院分区：
文献类型：
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作者：
Hasegawa, Sumitaka;Koshikawa-Yano, Michiko;Saga, Tsuneo
恶性间皮瘤（MM）是一种致命的恶性肿瘤，由于过去几个世纪石棉的广泛使用，在工业化国家发病率迅速上升。MM的早期诊断对于更好的预后至关重要，但由于缺乏疾病特异性诊断成像，这通常很困难。在这里，我们报告了锰增强磁共振成像（MEMRI）通过监测锰超氧化物歧化酶（Mn- sod）的高水平表达，代表了一种有希望的更具选择性的间皮瘤成像方法，这在许多MM中观察到。我们发现，与人间皮细胞相比，大多数人MM细胞过表达Mn- sod蛋白，NCI-H226人MM细胞在负载氯化锰（MnCl2）时高度表达Mn- sod并增强Mn积累。由于Mn2+对T-1的缩短作用，MnCl2培养后的细胞在体外MRI上显示出明显的T-1信号增强。在mncl2增强的t -1加权MR图像（T1WI）中，与肺腺癌细胞肿瘤和另一种人MM细胞肿瘤相比，H226皮下肿瘤优先增强，与它们各自的Mn-SOD表达水平相关。此外，在更具有临床相关性的环境中，H226异种移植胸膜肿瘤明显增强，并且使用临床使用的造影剂锰二磷酸（MnDPDP）和MnCl2， MEMRI很容易检测到。因此，我们提出MEMRI可以成为一种潜在的强大的无创检测MM的方法，具有高空间分辨率和显著的信号增强，通过靶向Mn-SOD。
Malignant mesothelioma (MM) is a fatal malignancy with a rapidly increasing incidence in industrialized countries because of the widespread use of asbestos in the past centuries. Early diagnosis of MM is critical for a better prognosis, but this is often difficult because of the lack of disease-specific diagnostic imaging. Here, we report that manganese-enhanced magnetic resonance imaging (MEMRI) represents a promising approach for a more selective mesothelioma imaging by monitoring a high-level expression of manganese-superoxide dismutase (Mn-SOD), which is observed in many MM. We found that most human MM cells overexpressed Mn-SOD protein compared with human mesothelial cells and that NCI-H226 human MM cells highly expressed Mn-SOD and augmented Mn accumulation when loaded with manganese chloride (MnCl2). The cells showed marked T-1-signal enhancement on in vitro MRI after incubation with MnCl2 because of the T-1 shortening effect of Mn2+. H226 subcutaneous tumor was preferentially enhanced compared with a lung adenocarcinoma cell tumor and another human MM cell tumor in MnCl2-enhanced T-1-weighted MR image (T1WI), correlating with their respective Mn-SOD expression levels. Moreover, in a more clinically relevant setting, H226 xenografted pleural tumor was markedly enhanced and readily detected by MEMRI using manganese dipyridoxyl diphosphate (MnDPDP), a clinically used contrast agent, as well as MnCl2. Therefore, we propose that MEMRI can be a potentially powerful method for noninvasive detection of MM, with high spatial resolution and marked signal enhancement, by targeting Mn-SOD.