Evaluation of Residual Disease After Neoadjuvant Chemotherapy Using Manganese-Enhanced Magnetic Resonance Imaging in an Orthotopic Mouse Model of Breast Cancer

Abstract

Purpose: This study compared the accuracy of manganese-enhanced magnetic resonance imaging (MRI) using hollow manganese silicate (HMS-MRI) to gadolinium-enhanced MRI (Gd-MRI) in predicting lesion size and residual tumor cellularity after chemotherapy using in vivo and in vitro experiments. Materials and Methods: BT474 cells and orthotopic xenograft mouse models of human breast cancer, based on BT474 cell inoculation, were used for the in vivo and in vitro experiments, respectively. Eighteen female mice underwent Gd-MRI and HMS-MRI before and after chemotherapy. The tumor size and residual tumor cellularity obtained from Gd-MRI and HMS-MRI after treatment were compared with the pathological findings. Differences in residual tumor size and cellularity measured by MRIs also correlated with the pathological findings. Two sets of BT474 cell pellets treated with or without chemotherapy were imaged after the addition of manganese chloride (MnCl2) or gadolinium. Results: Agreement in both tumor size and residual tumor cellularity between HMS-MRI and pathology was stronger than that between Gd-MRI and pathology. The lower the tumor–stroma ratio in pathological specimens, the larger was the difference in residual tumor cellularity between Gd-MRI and HMS-MRI (r = -0.62, p = 0.018). BT474 cell pellets showed signal enhancement after exposure to MnCl2, and the degree of enhancement decreased when the cell pellets were exposed to chemotherapeutic agents. Conclusion: HMS-MRI reflects residual tumor cellularity more accurately than Gd-MRI, especially in cases with low residual tumor cellularity.