Tumor response and tolerability under fractionated x-ray irradiation in a mouse xenograft model

Objective.Modern self-contained x-ray irradiators offer a safer alternative to radionuclide sources for preclinical radiation research and can deliver conformal, clinically relevant dose distributions. However, concerns persist regarding their performance and biological toxicity as direct replacements in radiobiological studies. We assessed two preclinical x-ray platforms, a collimated cabinet X-Rad320 and an image-guided small animal radiation research platform (SARRP), for induced tumor response, tolerability, and dosimetric accuracy in a subcutaneous xenograft prostate tumor model under 2 Gy daily fractionated radiotherapy.Approach.Male athymic mice bearing 22Rv1 xenografts were randomized into cohorts receiving total doses of 10, 16, or 20 Gy (5, 8, or 10 2-Gy fractions) on either platform. Unirradiated controls were included. Tumor burden was quantified by the area under the tumor growth curve (AUC). Machine dose delivery accuracy was verified quarterly with alanine pellet dosimetry.Main results.Across regimens, no animals met humane body condition or weight endpoints or exhibited overt clinical toxicity. All irradiated groups had lower tumor normalized AUCs than controls, but the dose response was not clearly monotonic, and not all differences remained statistically significant after correcting for multiple comparisons. At 14 d post-treatment, SARRP at 16 Gy provided the greatest tumor suppression, with no significant additional benefit observed with 20 Gy. Histologicalγ-H2AX staining provided complementary evidence of a radiation-induced dose response.Significance.Focused x-ray platforms can reproducibly deliver conventional fractionated radiotherapy regimens in mice, inducing tumor response without overt clinical toxicity. However, platform-specific dose deviations highlight the need for rigorous dosimetric calibration and quality assurance to ensure they can effectively replace cesium-137 forin vivoresearch with comparable tumor control outcomes.