Pharmacological agents for the prevention and treatment of toxic radiation exposure in spaceflight

Background Astronauts are exposed to toxic ionizing radiation sources, including galactic cosmic radiation and solar particle events (SPE). Exposure to these radiation sources can lead to cataracts, heritable genetic mutations, cancer, acute life-threatening physiological compromise, and death. Current countermeasures focus on spacecraft shielding and creation of heavily shielded safe havens. At issue is the extraordinarily high cost of launching these heavy structures into space and their inability to provide adequate shielding from heavy ions at a feasible shield thickness. Pharmacological enhancement of cellular radiation resistance, an alternative method to limiting radiation toxicity, has received less attention. Methods We have conducted an extensive literature review and critical evaluation of the scientific data pertaining to this field of study. Publications for review were identified through a Medline search using relevant terms, including radiotherapeutics, galactic cosmic radiation, radiopharmacology, radioprotectants, radiation countermeasures, solar particles, solar flares, radiation toxicity, and radiotoxicity. Results We identified 15 agents with significant radiation dose reduction factors, ranging from 1.1 to 2.4, in experimental models. Of these, only amifostine is FDA approved for use in treating radiation toxicity. Conclusions Current data do not support the use of radiopreventive agents in the treatment of low-level ionizing radiation exposures. However, pharmacological countermeasures should be instituted for life-threatening, high-level radiation exposures, as occur with SPE. Given the catastrophic effects of SPE, the risk of toxicity from radioprotective agents is warranted. The current data supports treatment with high-dose amifostine (at 910 mg m(-2)) 30 min prior to radiation exposure.