2013 Dade W. Moeller Lecture

Abstract

Soon after the 9–11 attacks, politicians and scientists began to question our ability to cope with a large-scale radiological terrorism incident. The outline of what was needed was fairly obvious: the ability to prevent such an attack; methods to cope with the medical consequences; the ability to clean up afterwards; and the tools to figure out who perpetrated the attack and bring them to justice. The medical response needed three components: the technology to rapidly determine the radiation doses received by a large number of people, methods for alleviating acute hematological radiation injuries, and therapies for mitigation and treatment of chronic radiation injuries. Research done to date has shown that a realistic medical response plan is scientifically possible, but the regulatory and financial barriers to achieving this may currently be insurmountable.

Metabolomic applications in radiation biodosimetry: exploring radiation effects through small molecules

“…Neupogen ® and Neulasta ® [filgrastim and polyethylene glycol (PEG)-filgrastim, respectively] have been approved as mitigators to increase survival of individuals exposed to doses that can lead to myelosuppression (Farese and MacVittie, 2015, Homer et al, 2016, Singh et al, 2016) and were developed with support from the National Institute of Allergy and Infectious Diseases (NIAID). Protectors, however, require prior knowledge of an incident and therefore can only be practically administered to first responders and military personnel (Coleman et al, 2012, Moulder, 2014). In addition, the FDA approved radioprotector Amifostine ® has a very narrow window for administration in order to protect normal tissue and is unfortunately associated with severe side effects (Singh et al, 2016).…”

Clinically Relevant Doses of Enalapril Mitigate Multiple Organ Radiation Injury

“…Second, ACE inhibitors may exacerbate radiation-induced gastrointestinal injury (26), so delaying the start of therapy until after the peak of acute gastrointestinal would be clinically appropriate. Finally, we are attempting to model a realistic scenario for accidental or belligerent radiation exposure where therapies could not be started immediately and probably would not be started until after preliminary dose estimation and triage (1). …”

“…Accidental or belligerent radiation exposures may result in significant lung and renal injuries (1). These will be especially important in subjects who have partial-body exposures that spare some bone marrow, thus averting death due to hematopoietic failure.…”

“…We use the term “mitigate” [as defined by the National Institutes of Health in 2004 (3)] to refer to therapies begun after irradiation, but before there is physiological evidence of injury. Subjects who survive radiation-induced pneumonitis (typically at 1–3 months after irradiation) will be at risk for radiation-induced nephropathy in the weeks and months after the exposures (1). It is not known whether ACEi will mitigate both injuries when they occur sequentially.…”

Addressing the Symptoms or Fixing the Problem? Developing Countermeasures against Normal Tissue Radiation Injury

“…An additional benefit would be an improvement in the quality of life of survivor populations, a growing concern at the National Cancer Institute (1, 2). At the other end of the spectrum are personnel affected by a mass casualty situation such as a deliberate or accidental nuclear or radiological event (3). Unlike approaches that might be of use in the highly defined clinical setting, countermeasures that would be utilized in an emergency event require broad activity since they will be targeted to radiation injuries resulting from, in all likelihood, relatively unknown dose exposures, involving heterogeneous volumes that may have affected multiple tissues and organs.…”