Magnetic drug targeting in a rhabdomyosarcoma rat model using magnetite-dextran composite nanoparticle-bound mitoxantrone and 0.6 tesla extracorporeal magnets - sarcoma treatment in progress

Background: Magnetic drug targeting (MDT) is a new treatment principle for tumors. Passive MDT (pMDT) uses cytostatics coupled to ferromagnetic nanoparticles, whereas in active MDT (aMDT), extracorporeal magnets are additionally placed over the tumor area. Purpose: Mitoxantrone-magnetite-dextran composite particles were used to assess the distribution and effect of MDT. Methods: We conducted two trials with n = 60 rats transfected with R1H rhabdomyosarcoma cells. In the biodistribution trial (n = 36) mitoxantrone concentrations in tumor tissue versus plasma were measured after one or two dose administration for aMDT, pMDT, and uncoupled mitoxantrone. The dose/effect trial (n = 24) assessed change in tumor volume at day 1 and 7 days after administration of 4, 6, or 8 doses of mitoxantrone using aMDT. Results: Mitoxantrone-magnetite-dextran concentration in blood was significantly (p < 0.05) lower when using aMDT and as low as uncoupled mitoxantrone. Concentrations in tumor tissue were always significantly higher using MDT when compared to uncoupled mitoxantrone. Two doses resulted in drug accumulation inside the tumor. Tumor growth was significantly decreased with four doses using aMDT versus no treatment. Tumor size on day 8 versus day 1 was significantly (p < 0.05) reduced after administration of six doses of mitoxantrone-magnetite-dextran. No allergies/toxic reactions were observed. Conclusions: The MDT achieves higher levels of cytostatics in tumor tissue without increased systemic concentrations and succeeds in reducing tumor volume.