Abstract 5524: Radiosensitization of nanoparticle-based thermal delivery in mice bearing human prostate cancer

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Abstract Heat is a potent sensitizer for radiation therapy. Technical hurdles associated with the selective and tumor-specific delivery of cytotoxic heat have precluded the widespread clinical adoption of heat as a therapeutic agent. Iron oxide magnetic nanoparticles have recently emerged as a promising alternative. Male nude mice bearing PC3 tumors, a human prostate cancer cell line, were used for the study. A total of fifteen cohorts of mice, with ten mice per group, were used. Five groups received nanoparticle thermal therapy (no radiation) at varying thermal doses; four groups received the combination of heat with 5 Gy radiation within five minutes post thermal therapy; three groups received radiation only (5, 8, and 10 Gy); and, three groups served as controls (no treat, magnetic field only, and particles with 5 Gy but no magnetic field). Magnetic nanoparticles suspensions were injected directly into the tumors at doses 5, 2.5, and 1 mg Fe/g tumor. Two to four hours post-injection, the mice were anesthetized and placed in a helical solenoid alternating magnetic field coil. Particle heating was initiated by an AC field with frequency of 160 kHz and varying amplitudes of 600, 500, and 400 Oersteds for twenty minutes. The particle heat output varies with field amplitude. Cohorts of mice receiving combined radiation and heat therapy were given 5 Gy radiation within five minutes of thermal therapy. Tumor growth was monitored and growth delay and survival was measured. Intratumor and rectal temperatures were monitored in five mice of each heat therapy cohort with optical fiber-based temperature probes. Complete tumor regression was observed for the 600 Oe and 5 mg Fe/g tumor combination, with local morbidity. Radiosensitization was achieved with lower thermal doses (400 Oe and 500 Oe with 5 mg Fe/g tumor) and no morbidity. For these cohorts, the heat alone was not effective. Tumor volume doubling time for 400 Oe and 5 mg Fe was 7 days (5 days for no treat control), and 10 days for 500 Oe and 5 mg Fe. However, the combination of 5 Gy (doubling time 22 days) with heat, even with the low thermal dose, produced significant tumor responses. For the combination of 400 Oe and 5 mg Fe with 5 Gy, tumor doubling time was increased to 32 days, and for the combination of 500 Oe with 5 mg Fe and 5 Gy, tumor volume failed to achieve doubling 45 days post therapy. Further study and analysis is ongoing and the results of their conclusions will be presented. Magnetic nanoparticle-based heat delivery has the potential to sensitize tumors to radiation even with low thermal doses. This offers the potential to improve therapeutic response while simultaneously minimizing therapy-related morbidity. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 5524.