Development of Radiation Countermeasures

Abstract

Medical countermeasures are required to address the emerging radiological and nuclear threats. Radiation injury can result from exposure to external, penetrating radiation or internalized radionuclides. Countermeasures for internal contamination focus on decorporation and protecting the primary site of activity. No countermeasures are currently approved for the acute radiation syndrome that results from external exposures, but significant efforts are ongoing to develop new agents to counter the cascade of damage from ionizing radiation. Antioxidants and enzyme mimics are directed toward prevention of free radical damage to macromolecules. Other agents target the affected cell‐signaling pathways: preventing apoptosis, triggering cell cycle arrest, or modulating the inflammatory response. To counter the loss of progenitor cells, particularly in the bone marrow and the gut, drugs such as the cytokines and other immunomodulators are developed to promote proliferation of new cells. If radiation injury proceeds to organ failure and infection, supportive care and antibiotics provide significant therapeutic value. In addition to the radiation dose, several factors impact the severity of the injury. Among these are radiation quality (e.g. neutron–gamma mixed fields) and dose rate, combined injuries, and partial‐body exposures. In future efforts, it will be important to consider these factors, which can modulate the radiation response and possibly affect the efficacy of the treatments. Although an ideal countermeasure that is inexpensive, stable with a long shelf‐life, easily administered, nontoxic, and efficacious is yet to be attained, new options continue to arise. Many promising drugs are in the pipeline.