MRI Contrast Enhancement Using Ferritin Genes and Its Application for Evaluating Anticancer Drug Efficacy in Mouse Melanoma Models

Abstract

The study aimed to introduce a ferritin gene probe into a mouse melanoma model to facilitate longitudinal in vivo monitoring of malignant melanoma via magnetic resonance imaging (MRI), thus creating a new prognostic tool and pharmacodynamic resource. B16 cells transfected with the human ferritin heavy chain (hFTH) and human ferritin light chain (hFTL) were subcutaneously inoculated into the dorsal areas of C57BL/6J mice for xenograft models. These xenograft models of malignant melanoma were monitored using the 4.7-T MRI system. Axial slices were acquired at the xenograft site, using T-2-weighted spin-echo and T-2*-weighted gradient-echo sequences. In addition, the efficacy of anticancer drugs was evaluated in the xenograft models. The hFTH- and hFTL-transfected B16 cells had significantly lower signal intensities in T-2- and T-2*-weighted MRI images than did the control group (w/o ferritin transfection). This was grossly correlated with tumor progression and could be visualized. The oregonin and oregonin + dacarbazine (DTIC) treated groups showed greater survival rates than the control and DTIC-only groups. We have developed an effective MRI contrast enhancement method using a ferritin gene probe. It can be applied reliably to evaluate the efficacy of drugs in preclinical and clinical trials, greatly assisting the development of new chemotherapeutics.