Manganese-enhanced MRI reveals early-phase radiation-induced cell alterations in vivo

For tumor radiotherapy, the in vivo detection of early cellular responses is important for predicting therapeutic efficacy. Mn(2+) is used as a positive contrast agent in manganese-enhanced MRI (MEMRI) and is expected to behave as a mimic of Ca(2+) in many biologic systems. We conducted in vitro and in vivo MRI experiments with Mn(2+) to investigate whether MEMRI can be used to detect cell alterations as an early-phase tumor response after radiotherapy. Colon-26 cells or a subcutaneously grafted colon-26 tumor model were irradiated with 20 Gy of X-rays. One day after irradiation, a significant augmentation of G2-M-phase cells, indicating a cell-cycle arrest, was observed in the irradiated cells in comparison with the control cells, although both early and late apoptotic alterations were rarely observed. The MEMRI signal in radiation-exposed tumor cells (R1: 0.77 ± 0.01 s(-1)) was significantly lower than that in control cells (R1: 0.82 ± 0.01 s(-1)) in vitro. MEMRI signal reduction was also observed in the in vivo tumor model 24 hours after irradiation (R1 of radiation: 0.97 ± 0.02 s(-1), control: 1.10 ± 0.02 s(-1)), along with cell-cycle and proliferation alterations identified with immunostaining (cyclin D1 and Ki-67). Therefore, MEMRI after tumor radiotherapy was successfully used to detect cell alterations as an early-phase cellular response in vitro and in vivo.