A Novel Cellular Imaging Method Using Hemagglutinating Virus of Japan-Envelope (HVJ-E) Vector and Magnetic Particle Imaging

摘要

The purpose of this study was to develop a novel cellular imaging method using the hemagglutinating virus of Japan-envelope (HVJ-E) vector and magnetic particle imaging (MPI). First, we determined the concentration of magnetic nanoparticles (MNPs) suitable for encapsulation into the HVJ-E vector (HVJ-MNPs). Colon-26 cells were labeled with HVJ-MNPs, MNPs conjugated with protamine (Pro-MNPs) or MNPs alone (Res-MNPs), and their labeling efficiencies were evaluated. Second, HVJ-MNPs, Pro-MNPs or Res-MNPs were injected directly into the tumors of tumor-bearing mice and the MPI images were obtained using our MPI scanner. The temporal change of the MNPs in the tumor was quantitatively evaluated by calculating the average MPI value. In addition, the microstructures of the resected tumor tissues were observed using a transmission electron microscope (TEM). The amount of iron encapsulated into HVJ-E and the encapsulation efficiency, saturated and decreased linearly with increasing amount of added iron, respectively. The labeling efficiency of HVJ-MNPs was significantly higher than those of Res-MNPs and Pro-MNPs. In animal studies, the average MPI value in the HVJ-MNP group remained almost constant up to 14 days, whereas those in the Res-MNP and Pro-MNP groups significantly decreased at 1 day or later, compared with that at 1 hour after the injection of the agents. In the TEM studies, earlier uptake of HVJ-MNPs in the cytoplasm was observed compared with Res-MNPs and Pro-MNPs. Our results suggest that the present method is useful for cellular imaging and tracking, and that HVJ-E is effective in internalizing MNPs into cells, during cellular imaging using MPI.