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Early Detection and Diagnosis
Molecular imaging of mesothelioma by detection of manganese-superoxide dismutase activity using manganese-enhanced magnetic resonance imaging
Article first published online: 8 JUL 2010
DOI: 10.1002/ijc.25547
Copyright © 2010 UICC
Additional Information
How to Cite
Hasegawa, S., Koshikawa-Yano, M., Saito, S., Morokoshi, Y., Furukawa, T., Aoki, I. and Saga, T. (2011), Molecular imaging of mesothelioma by detection of manganese-superoxide dismutase activity using manganese-enhanced magnetic resonance imaging. International Journal of Cancer, 128: 2138–2146. doi: 10.1002/ijc.25547
Publication History
- Issue published online: 8 MAR 2011
- Article first published online: 8 JUL 2010
- Accepted manuscript online: 4 AUG 2010 12:06PM EST
- Manuscript Accepted: 29 JUN 2010
- Manuscript Received: 26 FEB 2010
- Abstract
- Article
- References
- Cited By
Keywords:
- mesothelioma;
- molecular imaging;
- manganese;
- MRI;
- Mn-SOD
Abstract
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 T1-signal enhancement on in vitro MRI after incubation with MnCl2 because of the T1 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 T1-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.