Distribution of small magnetic particles in brain tumor-bearing rats

Small (10-20 nm) uncharged magnetic particles (SMP) were evaluated for their ability to target intracerebral rat glioma-2 (RG-2) tumors in vivo. In an effort to determine the influence of particle size on blood-tumor barrier uptake, the tissue distribution of the injected particles was evaluated following intraarterial injection (4 mg/kg SMP) in male Fisher 344 rats bearing RG-2 tumors with a magnetic field of 0 G or 6000 G applied to the brain for 30 min. Animals were sacrificed at 30 min or 6 h post-injection after which tissues were collected and analyzed for magnetite content. In the presence of a magnetic field, SMP localized in brain tumor tissue at levels of 41-48% dose/g tissue after 30 min and 6 h respectively, significantly greater than non-target tissues. In the absence of a magnetic field only 31-23% dose/g tissue was achieved for the same time points. Tumor targeting of the SMP for brain tumor was demonstrated by large target selectivity indexes (t(s)) of 2-21 for normal brain tissue, indicating a 2-21 fold increase in concentrations compared to normal brain. In comparison with larger (1 mu m) diameter magnetic particles, SMP concentrated in brain tumor at significantly higher levels than magnetic neutral dextran (p = 0.0003) and cationic aminodextran (p = 0.0496) microspheres previously studied. TEM analysis of brain tissue revealed SMP in the interstitial space of tumors, but only in the vasculature of normal brain tissue. These results suggest that changes in the vascular endothelium of tumor tissue promote the selective uptake of SMP and provide a basis for the design of new small drug-loaded particles as targeted drug delivery systems for brain tumors.