NOD-SCID mice irradiation with medical accelerators: Dosimetric and radiobiological results

Abstract

Purpose: Preclinical studies normally requires dedicated instruments due to the small anatomical scales involved, but the possibility of using clinical devices for this purpose may be of economical, scientific and translational interest. In the present work the accurate description of treatment planning, dosimetric results, radiotoxicity and tumor response of the irradiation of NOD-SCID mice were presented. Two medical linear accelerators, TrueBeam STx and Tomotherapy Hi-ART, were compared. NOD-SCID mice irradiation with Tomotherapy is a novelty, as well as the comparison of different irradiation techniques, devices and dose fractionations.

Methods: Human derived glioblastoma multiforme neurospheres were injected in immunocompromised NOD-SCID mice to establish xenograft models. Mice were anaesthetized and placed in a plexiglas cage pieboth to perform CT scan for treatment planning purposes and for the irradiation. Three fractionation schedules were evaluated: 4Gy/1 fraction, 4Gy/2 fractions and 6Gy/3 fractions. Tomotherapy planning parameters, the presence of a bolus layer and the irradiation time were reported. After irradiation, mice were examined daily and sacrificed when they showed signs of suffering or when tumor volume reached the established endpoint. Outcomes regarding both radiotoxicity and tumor response were evaluated comparing irradiated mice as respect to their controls.

Results: Survival analysis showed that Tomotherapy irradiation with 6Gy/3 fractions with a bolus layer prolong mice survival (log-rank test, p<0.02). Tumor volume and mice survival were significantly different in irradiated xenografts as compared to their controls (t-test, p<0.03; log-rank, p<0.05).

Conclusion: The radiobiological potential of Tomotherapy in inducing tumor growth stabilization is demonstrated.

Keywords: Linacs; NOD-SCID mice; Toxicity; Tumor response.