Abstract 1403: Harnessing nanoparticles to improve toxicity after head and neck radiation
Authors: Manon Rafael , Madero-Visbal Rafael , Colon Jimmie F. , Alvarado Beatrice , Wason Melissa , Kupelian Patrick , Baker Cheryl H. 
Published: February 2011

PURPOSE: To evaluate the ability of cerium oxide nanoparticles (CeO2) to decrease xerostomia and skin reactions in athymic mice.

METHODS: The head and neck (H&N) region of athymic nude mice was irradiated using a IC160 X-ray irradiation system (Kimtron Inc., Woodbury, Connecticut, USA). Animals were anesthetized and placed supine under the radiation focal spot. Irradiation was given with a single AP portal using a 160 kV X-ray unit. Three radiation cohorts were designed (N=30 per cohort); A) received no radiation exposure; B) received a single dose of 17.5 Gy; and C) received 30 Gy/6 fractions. In each cohort, animals were randomized into three groups (N=10 per group): 1) intraperitoneal (i.p.) injection of saline; 2) i.p. injection of 15 nM CeO2; and 3) i.p. injection of 15 µM CeO2. Two independent double-blinded researchers graded radiation-induced dermatitis and hyperpigmentation at 1, 4, and 12 weeks after radiation therapy according to CTC v. 3.0 criteria. Ninety days after radiation, all mice were anesthetized and stimulated salivary flow was measured after subcutaneous pilocarpine injection (2mg/kg of B.W.)

RESULTS: Stimulated sialometry strongly demonstrated improved salivary production in all CeO2 groups compared to controls not receiving CeO2 (mean salivary flow 204 vs. 115 µL/10min p=.0002). Grade 3 dermatitis was more prevalent in the fractionated vs. the single fraction cohort. In the fractionated cohort, the incidence of grade 3 dermatitis 1 week after radiation was decreased in the 15 µM CeO2 group compared to the non-CeO2 controls (10% vs. 100% incidence of Grade 3 dermatitis, respectively). A similar effect in reduction of grade 3 dermatitis was seen in the 15 µM CeO2 group when compared to non-CeO2 controls in both radiation cohorts for all time points evaluated. This effect was not appreciated in the 15 nM CeO2 group. There was decrease in skin hyperpigmentation at 12 weeks in the 15 µM CeO2 group compared to the 15 nM CeO2 and non-CeO2 groups (50, 70, and 90% grade 2, respectively). There were four Grade V toxicities in the fractionated cohort; three in the 15 nM CeO2 group and one in the non-CeO2 group. No Grade V toxicities were noted in the 15 µM CeO2 group of mice. Additionally, there were no adverse effects noted in the groups of mice receiving CeO2 without radiation.

CONCLUSIONS: This study suggests that cerium oxide nanoparticles may have a radiation protective effect on salivary production. Parallel observations indicate a reduction in Grade 3 radiation-induced dermatitis and skin hyperpigmentation. The use of cerium oxide nanoparticles as a radioprotectant may be a feasible concept, but should be tested in a larger cohort of mice using a 15 µM concentration of CeO2.

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 1403.