Only two radioprotective compounds, amifostine and palifermin, currently have the US FDA approval for use in radiation therapy. However, several agents have been reported that show therapeutic promise. Many of these agents are free radical scavengers/antioxidants. Superoxide dismutase and superoxide dismutase mimetics, nitroxides and dietary antioxidants are all being investigated. Recently, alternative strategies of drug development have been evolving, which focus on targeting the series of cellular insult recognition/repair responses initiated following radiation. These agents, which include cytokines/growth factors, angiotensin-converting enzyme inhibitors and apoptotic modulators, show promise of having significant impact on the mitigation of radiation injury. Herein, we review current literature on the development of radioprotectors with emphasis on compounds with proven or potential usefulness in radiation therapy.

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Purpose: Repair kinetics of radiation damage in mouse lung remains controversial. Using the generalized LQ (gLQ) model that was developed to address the dilemma of the LQ model in high dose range we investigate repair kinetics of mouse lung to radiation. Methods: In an animal study (Vegesna et al. Radiother Oncol 1989; 15:115), mouse lungs were irradiated with repeated dose from 1.6 Gy to 14.3 Gy. The endpoint was death due to radiation pneumonitis. A repair half‐time T1/2=1.5 hour derived from the data of reciprocal of LD50 (lethal dose for 50% mortality) vs. dose‐per‐fraction was much longer than the repair half‐time of 0.4 hour published in the literature. In this study, the same dataset was reanalyzed by using both the LQ and the gLQ models. The least χ2 method was adopted to fit the data and to evaluate the merit for the two models. Results: The combined repair half‐times of 0.4 and 4 hour were used in the gLQ and LQ models, the gLQ model fit the data better than the LQ model: the reduced χ2 is 0.46 vs. 3.8, and α/ß is 2.4 vs. 2.6, respectively. However, when only the fast mode of repair time (0.4 hour) was used, the LQ model couldn't produce the downward curvature based on the low dose data while the gLQ predicted well the high dose data. The gLQ model fit the data much better than the LQ model: the reduced khgr;2 is 0.16 vs. 2.3, and α/ß is 2.4 vs. 3.0, respectively, yielding the consistent α/ß ratio. Conclusions: The gLQ model provides a consistent interpretation of the mouse lung data across fraction sizes up to 14 Gy. Therefore, the gLQ model is able to extend our clinical experience accumulated from conventional low‐dose fractionation to high dose irradiation schedules, including SRS/SBRT and HDR brachytherapy.

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