In vivo MRI Follow-up of Murine Tumors Treated by Electrochemotherapy and other Electroporation-based Treatments

Abstract

In vivo cell electropermeabilization can be used alone or in combination with a hydrophilic, nonpermeant cytotoxic drug such as bleomycin (electrochemotherapy) to efficiently treat tumors. We used magnetic resonance imaging to detect rapid structural modifications in tumors treated by electroporation-based methods. Water diffusion coefficient (ADC), transverse relaxation time (T2) and tumor volume of fibrosarcomas xenografted on syngenic mice were measured upon 3 groups of 6 treated mice within the 48 hrs following ECT done with a normal (BE) or a high dose of bleomycin (HBE), and after irreversible electroporation (IRE), and in three control groups. As expected, the tumor volume increased in the control groups at 48 hrs (p < 0.05) and the values of ADC and T2 did not varied significantly in the control groups except for ADC decrease and T2 increase observed between 3 hrs and 24 hrs (p < 0.03) in the group that received bleomycin only. Tumor volumes decreased significantly at 24 hrs in the IRE and HBE groups. The mean tumor ADC increased significantly at 24 hrs (+17.6%, p < 0.03) in the BE group, probably reflecting apoptosis, while in the HBE group the mean tumor ADC increased earlier, at 10 hrs (+19%, p < 0.03) because of the speed of the pseudoapopototic process. In the IRE group, the mean tumor ADC decreased significantly at 1 hrs (p < 0.05) and 3 hrs (p < 0.03), and T2 decreased (p < 0.03), both probably reflecting cell swelling induced by the vascular lock. Thus ADC and T2 changes in the treated tumors correlated with previous histological observations on the same tumor models. Noteworthy, ADC allowed the visualization of early and rapid changes in the treated tumors, when tumor volume monitoring was not yet able to detect any effect of the treatments.