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.