Pharmacological management of ionizing radiation injuries: current and prospective agents and targeted organ systems

ABSTRACT

Introduction: There is a limited array of currently available medicinals that are useful for either the prevention, mitigation or treatment of bodily injuries arising from ionizing radiation exposure.

Area covered: In this brief article, the authors review those pharmacologic agents that either are currently being used to counter the injurious effects of radiation exposure, or those that show promise and are currently under development.

Expert opinion: Although significant, but limited progress has been made in the development and fielding of safe and effective pharmacotherapeutics for select types of acute radiation-associated injuries, additional effort is needed to broaden the scope of drug development so that overall health risks associated with both short- and long-term injuries in various organ systems can be reduced and effectively managed. There are several promising radiation countermeasures that may gain regulatory approval from the government in the near future for use in clinical settings and in the aftermath of nuclear/radiological exposure contingencies.

KEYWORDS:

• Acute radiation syndrome
• chronic/delayed radiation injuries
• cytokines
• growth factors
• irradiation
• pharmacological agents
• radiation countermeasures

Acknowledgments

The opinions or assertions contained herein are the private views of the authors and are not necessarily those of the Uniformed Services University of the Health Sciences, or the Department of Defense. Mention of specific therapeutic agents does not constitute endorsement by the US Department of Defense, and trade names are used only for the purpose of clarification.

Declaration of interest

The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Article highlights

• There are only three FDA-approved radiation countermeasures for ARS (Neupogen, Neulasta, and Leukine) and all are radiomitigators for H-ARS.

• Currently, no radioprotector for either H-ARS or for GI-ARS has been approved by the FDA for human use.

• There are four agents which have been approved as blocker, binder or chelator (ThyroShield, Radiogardase, Zn-DTPA, and Ca-DTPA) by FDA for internalized radionuclides.

• There are several radiation countermeasures for various sub-syndromes under development that are considered safe and efficacious, however, they have not yet received FDA approval and need additional studies.

• Poly-pharmacy is an important approach that uses suboptimal doses of two or more countermeasures with different mechanisms of action to avoid side effects/toxicity and improve the treatment outcome.

• Repurposing is another useful approach where FDA-approved agents for one indication are deployed for another indication and such strategy significantly reduces the cost for storing the countermeasures in strategic national stockpile/vendor managed inventory.

• There is a need for additional FDA-approved agents for delayed, late, and chronic effects of radiation.

This box summarizes key points contained in the article.

Additional information

Funding

The authors gratefully acknowledge the research support from the National Institute of Allergy and Infectious Diseases (AAI12044‐001‐07000, Work plan G) to VK Singh.