A review of radiation countermeasures focusing on injury-specific medicinals and regulatory approval status: part I. Radiation sub-syndromes, animal models and FDA-approved countermeasures

Abstract

Purpose: The increasing global risk of nuclear and radiological accidents or attacks has driven renewed research interest in developing medical countermeasures to potentially injurious exposures to acute irradiation. Clinical symptoms and signs of a developing acute radiation injury, i.e. the acute radiation syndrome, are grouped into three sub-syndromes named after the dominant organ system affected, namely the hematopoietic, gastrointestinal, and neurovascular systems. The availability of safe and effective countermeasures against the above threats currently represents a significant unmet medical need. This is the first article within a three-part series covering the nature of the radiation subsyndromes, various animal models for radiation countermeasure development, and the agents currently approved by the United States Food and Drug Administration for countering the medical consequences of several of these prominent radiation exposure-associated syndromes. Conclusions: From the U.S. and global perspectives, biomedical research concerning medical countermeasure development is quite robust, largely due to increased government funding following the 9/11 incidence and subsequent rise of terrorist-associated threats. A wide spectrum of radiation countermeasures for specific types of radiation injuries is currently under investigation. However, only a few radiation countermeasures have been fully approved by regulatory agencies for human use during radiological/nuclear contingencies. Additional research effort, with additional funding, clearly will be needed in order to fill this significant, unmet medical health problem. ARTICLE HISTORY

Romiplostim (Nplate®) as an effective radiation countermeasure to improve survival and platelet recovery in mice

“…This hematopoietic subsyndrome of acute radiation syndrome (H-ARS) is characterized by dose-dependent bone marrow destruction leading to rapid depletion of white blood cells, platelets, and reticulocytes (i.e. lymphocytopenia, neutropenia, thrombocytopenia, and anemia) (Singh and Seed 2017). Such damage to the hematopoietic system can lead to lethality from infections, hemorrhages, and poor wound healing.…”

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

“…The injurious effects of radiation on hematopoiesis have been well studied in various animal models [12]. The three animal models extensively used in the majority of studies are mice, canines, and nonhuman primates (NHPs [19], and NHPs [2,[19][20][21]. Because G-CSF is not species-specific like GM-CSF, a majority of these studies have been accomplished using human recombinant G-CSF.…”

“…Amifostine is the only agent classified as a cytoprotectant and is approved for narrow clinical indications associated with radiotherapy and chemotherapy [76,77]. Furthermore, there are several cytokines and growth factors (palifermin (keratinocyte growth factor), erythropoietin (Epoetin/Epogen/ Procrit/Darbepoetin/Aransep), IL-3, IL-11 (Oprelvekin)) which have been approved by the FDA for limited indications (mostly cancer patients receiving chemotherapy and/or radiotherapy) [2,44,45].…”

“…Radiation mitigators are needed for mass casualty scenarios while radioprotectors will be helpful in radiotherapy and use for soldiers in anticipation of radiation exposure. Lastly, radiation therapeutics are used once symptoms of radiation exposure manifest [2].…”

The efficacy and safety of amifostine for the acute radiation syndrome

“…These agents are approved specifically for a major ARS subsyndrome, known as the hematopoietic sub-syndrome of ARS (H-ARS) [11][12][13][14][15][16][17]. It is important to note that at the present time no radioprotector for either H-ARS or for gastrointestinal-ARS (GI-ARS) has been approved by the FDA [18].…”