Request for Information (RFI): Mechanisms, Detection and Countermeasure Research and Development for Mixed-Field Radiation Exposure

Notice Number: NOT-AI-12-015

Key Dates

Release Date: November 3, 2011
Receipt Date: February 3, 2012

Issued by

National Institute of Allergy and Infectious Diseases (NIAID)


The growing threat of nuclear terrorism has highlighted the need for research and development of medical countermeasures (MCMs) to treat and/or mitigate injuries in the U.S. civilian population following a radiation incident. Individuals in the vicinity of the detonation of an improvised nuclear device (IND) could potentially be exposed to gamma irradiation (for which mechanisms of injury and expected medical effects are currently being researched and elucidated), and to mixed-field radiation (containing both neutron and gamma components). One possible scenario for an IND includes a detonation using highly enriched uranium, which produces significant neutron and gamma radiation components1. In such a scenario, depending on the individual’s position relative to the detonation, the prompt exposure could be mixed-field radiation. There are currently no medical countermeasures approved by FDA for the post-exposure treatment or mitigation of radiation injury. In addition, rapid identification of exposed individuals requiring treatment has not yet been achieved. There is, therefore, a need to evaluate and understand the specific injuries and mechanisms of injuries unique to mixed field radiation exposure; to develop medical countermeasures to treat and/or mitigate mixed field exposure injuries; and to develop methods and devices to identify individuals exposed to mixed field radiation. Through this Request for Information (RFI), the National Institute of Allergy and Infectious Diseases (NIAID) Radiation/Nuclear Countermeasures Program seeks information on the state of science in MCM development, biodosimetry techniques, and animal model development with regard to exposure to mixed-field radiation. There is also interest in the medical effects of, and appropriate biodosimetry for mixed-field radiation exposure in special populations such as children, the elderly, pregnant and lactating women and immuno-compromised individuals. The National Institutes of Health (NIH) will use the information obtained in response to this RFI to 1) develop recommendations for future research funding, 2) obtain a better understanding of the biological responses to neutron exposure, 3) encourage the development of biodosimetry devices to rapidly and accurately triage populations exposed to mixed-field irradiation, and 4) encourage research on effective and safe radiation MCMs for mixed-field exposures.


The Department of Health and Human Services (HHS) is charged with protecting the civilian population by providing leadership in research, development, acquisition, deployment, and use of effective MCM for Weapons of Mass Destruction. The HHS Public Health Emergency Medical Countermeasures Enterprise Implementation Plan for Chemical, Biological, Radiological and Nuclear (CBRN) Threats (HHS PHEMCE Implementation Plan) 2 provides a blueprint for all of its MCM-related activities, from research and development, to acquisition, storage, deployment and utilization. Among the top priorities identified by the HHS PHEMCE Implementation Plan are MCMs against radiological and nuclear threats. The NIAID, NIH has been tasked to develop and manage a comprehensive research and early to mid-stage product development program focused on medical therapies and diagnostics, as set by NIH Strategic Plan and Research Agenda for Medical Countermeasures against Radiological and Nuclear Threats3.

It has been estimated that following a 10 kiloton nuclear detonation, a significant number of people would be exposed to prompt radiation (and possibly mixed neutron and gamma fields) within about 0.5 miles of the site of detonation4. The ratio of neutron to gamma radiation exposure could vary due to shielding of the body, distance from the blast and type of weapon used. Individuals close to the blast may experience injuries that will be immediately obvious (e.g. burns, wounds, fractures, and trauma), while others may experience a more slowly-evolving illness, developing over weeks, months or even years following the incident. Currently, most Radiation/Nuclear MCM research focuses on the detection and treatment/mitigation of injuries resulting from exposure to gamma radiation and little is known about the biological responses to mixed-field radiation exposures. For example, some data indicate that sepsis that follows radiation injury differs between animals that have been irradiated with pure gamma versus mixed-field radiation5, and other, large animal studies find that lethality, as well as other clinical manifestations following neutron-gamma exposures are different from those of gamma exposure alone6. In order to effectively treat individuals who have been exposed to mixed-field radiation, it is critical to first understand more about how biological responses to mixed-field exposures differ from exposures to gamma radiation alone. Neutrons have different mechanisms of injury than gamma photons, causing more complex DNA damage which is more difficult to repair. This results in a higher relative biological effectiveness (RBE) for neutrons over gamma radiation7. These mechanistic differences may also alter the efficacy of medical countermeasures for neutron radiation-exposed individuals. Beyond the molecular level, rapidly proliferating cell-renewal systems are most vulnerable to neutron radiation injury, resulting in acute radiation syndromes, such as gastrointestinal and hematopoietic injuries. Because little recent work has been done on the effects of mixed-field radiation exposure, much work, including the most basic research into biological responses, injury/repair, biodosimetry and countermeasure development are needed. NIAID is interested in the following research areas of mixed-field radiation exposure:

1. Post-exposure mitigator/therapeutic drugs for mixed field injury (administered at least 24 hours after exposure)

2. Mechanisms of mixed field radiation injury and host signal transduction and repair responses;

3. High-throughput drug-screening assays to identify mitigators and radiotherapeutics for mixed-field injury;

4. Small and large animal model development for mixed-field exposure, for potential Food and Drug Administration (FDA) licensure via the Animal Rule8;

5. Automated, biology-based diagnostic assays/devices specific for rapid, accurate and non-invasive measurement of mixed-field (gamma and neutron) radiation exposure and injury;

6. Predictive, organ-specific biodosimetry specific to mixed-field exposure

7. Radiation combined injury (ie. mixed field radiation exposure plus other trauma)

8. Research into the early and late effects resulting from exposures to mixed-field radiation (e.g. lung, skin, kidney, cardiovascular, central nervous system complications); and

9. Radiation responses and MCM efficacy in special populations that have been exposed to mixed-field irradiation (e.g. pediatrics, geriatric, and/or immuno-compromised individuals).

This RFI is for planning purposes only and should not be construed as a solicitation for applications or as an obligation on the part of the Government to provide support for any identified opportunities. Please note that the Government will not pay for response preparation or the use of any information contained therein. Responses to this RFI are voluntary. Acknowledgement of receipt of responses will not be made. No basis for claims against the NIAID shall arise as a result of a response to this request for information or the NIAID’s use of such information as either part of our evaluation process or in developing specifications for any subsequent announcement. The Government reserves the right to use any non-proprietary technical information in any resultant solicitation(s). As previously indicated, the NIAID may use the information gathered to develop grant, contract, or other funding initiatives pending availability of funds. Any proprietary information should be so marked.

1. Garwin RL. A Nuclear Explosion in a City or an Attack on a Nuclear Reactor. The Bridge. Summer 2010; 40(2):20 27

2. (Accessed 07/25/11)

3. (Accessed 07/25/11)

4. Tenforde TS, Schauer DA, Goans RE, Mettler Jr. FA, Pellmar TC, Poston Sr. JW, and Taylor TP Health Aspects of a Nuclear or Radiological Attack. The Bridge. Summer 2010; 40(2): 50-57.

5. Elliott TB, Ledney GD, Harding RA, Henderson PL, Gerstenberg HM, Rotruck JR, Verdolin MH, Stille CM, Krieger AG. Mixed-field neutrons and gamma photons induce different changes in ileal bacteria and correlated sepsis in mice. Int J Radiat Biol. 1995 Sep;68(3):311-20.

6. Kuhn, US, Kyner, RE, Brown, DG. Response of Burros to Mixed Neutron and Gamma Irradiation. J. Radiat. Res., 1964 Sep;23(1):78-93.

7. Ward, JF. The complexity of DNA damage: relevance to biological consequences. Int J Radiat Biol. 1994 April; 66:427-432.

8. .9 (Accessed 07/25/11)


Information must be submitted by February 3, 2012. Responses should be limited to 10 pages and marked with this RFI identifier (NOT-AI-12-015). Responses are preferred in electronic format and can be e-mailed to the attention of:

Ms. Mai-Kim Norman, MS
Public Health Analyst, DAIT, NIAID, NIH, DHHS
6610 Rockledge Drive, Room 5304
Bethesda, MD  20892-7612
Phone:  30-451-3133
Fax:  301-480-6597