Molecular imaging of mesothelioma by detection of manganese-superoxide dismutase activity using manganese-enhanced magnetic resonance imaging

被引:14
|
作者
Hasegawa, Sumitaka [1 ]
Koshikawa-Yano, Michiko [1 ]
Saito, Shigeyoshi [1 ,2 ]
Morokoshi, Yukie [1 ]
Furukawa, Takako [1 ]
Aoki, Ichio [1 ]
Saga, Tsuneo [1 ]
机构
[1] Natl Inst Radiol Sci, Mol Imaging Ctr, Inage Ku, Chiba 2638555, Japan
[2] Tohoku Univ, Grad Sch Med, Aoba Ku, Sendai, Miyagi 980, Japan
基金
日本学术振兴会;
关键词
mesothelioma; molecular imaging; manganese; MRI; Mn-SOD; PLEURAL MESOTHELIOMA; GENE-EXPRESSION; LUNG-CANCER; MRI; METASTASIS; REPORTER; THERAPY; COPPER; AGENT; MEMRI;
D O I
10.1002/ijc.25547
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
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.
引用
收藏
页码:2138 / 2146
页数:9
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