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

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 (MnCl(2)). The cells showed marked T(1)-signal enhancement on in vitro MRI after incubation with MnCl(2) because of the T(1) shortening effect of Mn(2+). H226 subcutaneous tumor was preferentially enhanced compared with a lung adenocarcinoma cell tumor and another human MM cell tumor in MnCl(2)-enhanced T(1)-weighted MR image (T(1)WI), 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 MnCl(2). 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.

Tumor enhancement effect of overexpressed manganese-superoxide dismutase in manganese-enhanced MR imaging.

PURPOSE: Manganese-enhanced magnetic resonance imaging (MEMRI), used to trace neuronal connections and visualize brain activity, has recently been suggested useful for tumor detection, but the mechanism of tumor enhancement by manganese (Mn) is poorly understood. Our recent report of preferential enhancement of human mesothelioma cells with higher levels of manganese-superoxide dismutase (Mn-SOD) expression may suggest a correlation between Mn-SOD expression and enhancement. We investigate this possibility further using engineered human ovarian cancer cells overexpressing Mn-SOD. METHODS: We subcutaneously implanted SK-OV-3 human ovarian cancer cells stably overexpressing Mn-SOD (SK-Mn-SOD) into athymic nude mice and SK-OV-3 cells with plasmid DNAs carrying neomycin-resistant genes (SK-neo) into the same mice for controls. We conducted MEMRI in the tumor-bearing mice and compared enhancement between the 2 tumors. RESULTS: Subcutaneous SK-Mn-SOD tumors were preferentially enhanced in MEMRI compared to SK-neo tumors. After Mn enhancement, the T(1)-relaxation rate (R(1)=1/T(1)) increased significantly for SK-Mn-SOD but not SK-neo tumors. CONCLUSION: In some tumors, high expression of Mn-SOD may be a biological factor responsible for enhanced signal in MEMRI.