2,874
Views
27
CrossRef citations to date
0
Altmetric
Review

Medical countermeasures for unwanted CBRN exposures: part II radiological and nuclear threats with review of recent countermeasure patents

, , &
Pages 1399-1408 | Received 06 May 2016, Accepted 21 Jul 2016, Published online: 09 Sep 2016

References

  • Moulder JE. 2013 Dade W. Moeller lecture: medical countermeasures against radiological terrorism. Health Phys. 2014;107:164–171.
  • Bushberg JT, Kroger LA, Hartman MB, et al. Nuclear/radiological terrorism: emergency department management of radiation casualties. J Emerg Med. 2007;32:71–85.
  • Hall EJ, Giaccia AJ. Radiobiology for the radiobiologist. 7th ed. Philadelphia, PA: Lippincott Williams and Wilkins; 2012.
  • Flynn DF, Goans RE. Nuclear terrorism: triage and medical management of radiation and combined-injury casualties. Surg Clin North Am. 2006;86:601–636.
  • Stone HB, Coleman CN, Anscher MS, et al. Effects of radiation on normal tissue: consequences and mechanisms. Lancet Oncol. 2003;4:529–536.
  • Waselenko JK, MacVittie TJ, Blakely WF, et al. Medical management of the acute radiation syndrome: recommendations of the strategic national stockpile radiation working group. Ann Intern Med. 2004;140:1037–1051.
  • DiCarlo AL, Maher C, Hick JL, et al. Radiation injury after a nuclear detonation: medical consequences and the need for scarce resources allocation. Disaster Med Public Health Prep. 2011;5(Suppl 1):S32–S44.
  • Dainiak N, Waselenko JK, Armitage JO, et al. The hematologist and radiation casualties. Hematol Am Soc Hematol Educ Program. 2003;2003:473–496.
  • Anno GH, Young RW, Bloom RM, et al. Dose response relationships for acute ionizing-radiation lethality. Health Phys. 2003;84:565–575.
  • Allio T. Product development under FDA’s Animal Rule: understanding FDA’s expectations and potential implication for traditional development programs. Therap Inno Regul Sci. Forthcoming 2016. doi: 10.1177/2168479016641717
  • Singh VK, Newman VL, Berg AN, et al. Animal models for acute radiation syndrome drug discovery. Expert Opin Drug Discov. 2015;10:497–517.
  • Gronvall GK, Trent D, Borio L, et al. The FDA animal efficacy rule and biodefense. Nat Biotechnol. 2007;25:1084–1087.
  • Singh VK, Newman VL, Romaine PL, et al. Radiation countermeasure agents: an update (2011-2014). Expert Opin Ther Pat. 2014;24:1229–1255 .
  • Singh VK, Romaine PL, Newman VL. Biologics as countermeasures for acute radiation syndrome: where are we now? Expert Opin Biol Ther. 2015;15:465–471.
  • Singh VK, Newman VL, Seed TM. Colony-stimulating factors for the treatment of the hematopoietic component of the acute radiation syndrome (H-ARS): a review. Cytokine. 2015;71:22–37.
  • Hankey KG, Farese AM, Blaauw EC, et al. Pegfilgrastim improves survival of lethally irradiated nonhuman primates. Radiat Res. 2015;183:643–655 .
  • Singh VK, Pollard HB. Patents for Toll-like receptor ligands as radiation countermeasures for acute radiation syndrome. Expert Opin Ther Pat. 2015;25:1085–1092.
  • Pellmar TC, Rockwell S. Priority list of research areas for radiological nuclear threat countermeasures. Radiat Res. 2005;163:115–123.
  • Dainiak N. Hematologic consequences of exposure to ionizing radiation. Exp Hematol. 2002;30:513–528.
  • Cerveny TJ, MacVittie TJ, Young RW. Acute radiation syndrome in humans. In: Walker RI, Cerveny TJ, editor. Medical consequences of nuclear warfare, textbook of military medicine. Falls Church, VA: TMM Publications, Office of the Surgeon General Publications; 1989. p. 15–36.
  • Gusev IA, Guskova AK, Mettler FA. Medical management of radiation accidents. Boca Raton, FL: CRC Press; 2001.
  • Singh VK, Romaine PL, Seed TM. Medical countermeasures for radiation exposure and related injuries: characterization of medicines, FDA-approval status and inclusion into the strategic national stockpile. Health Phys. 2015;108:607–630.
  • Farese AM, MacVittie TJ. Filgrastim for the treatment of hematopoietic acute radiation syndrome. Drugs Today (Barc). 2015;51:537–548.
  • Singh VK, Newman VL, Romaine PL, et al. Use of biomarkers for assessing radiation injury and efficacy of countermeasures. Expert Rev Mol Diagn. 2016;16:65–81.
  • Esbitt D. The strategic national stockpile: roles and responsibilities of health care professionals for receiving the stockpile assets. Disaster Manag Response. 2003;1:68–70.
  • Need JT, Mothershead JL. Strategic national stockpile program: implications for military medicine. Mil Med. 2006;171:698–702.
  • Moroni M, Ngudiankama BF, Christensen C, et al. The Gottingen minipig is a model of the hematopoietic acute radiation syndrome: G-colony stimulating factor stimulates hematopoiesis and enhances survival from lethal total-body gamma-irradiation. Int J Radiat Oncol Biol Phys. 2013;86:986–992.
  • Nash RA, Schuening FG, Seidel K, et al. Effect of recombinant canine granulocyte-macrophage colony-stimulating factor on hematopoietic recovery after otherwise lethal total body irradiation. Blood. 1994;83:1963–1970.
  • MacVittie TJ, Farese AM, Jackson WI 3rd. Defining the full therapeutic potential of recombinant growth factors in the post radiation-accident environment: the effect of supportive care plus administration of G-CSF. Health Phys. 2005;89:546–555.
  • Schuening FG, Appelbaum FR, Deeg HJ, et al. Effects of recombinant canine stem cell factor, a c-kit ligand, and recombinant granulocyte colony-stimulating factor on hematopoietic recovery after otherwise lethal total body irradiation. Blood. 1993;81:20–26.
  • Patchen ML, MacVittie TJ. Granulocyte colony-stimulating factor and amifostine (Ethyol) synergize to enhance hemopoietic reconstitution and increase survival in irradiated animals. Semin Oncol. 1994;21:26–32.
  • Sureda A, Kadar E, Valls A, et al. Granulocyte colony-stimulating factor administered as a single intraperitoneal injection modifies the lethal dose (95/30) in irradiated B6D2F1 mice. Haematologica. 1998;83:863–864.
  • Hosoi Y, Kurishita A, Ono T, et al. Effect of recombinant human granulocyte colony-stimulating factor on survival in lethally irradiated mice. Acta Oncol. 1992;31:59–63.
  • Sureda A, Valls A, Kadar E, et al. A single dose of granulocyte colony-stimulating factor modifies radiation-induced death in B6D2F1 mice. Exp Hematol. 1993;21:1605–1607.
  • Mac Vittie TJ, Monroy RL, Vigneulle RM. The relative biological effectiveness of mixed fission-neutron-gamma radiation on the hematopoietic syndrome in the canine: effect of therapy on survival. Radiat Res. 1991;128:S29.
  • Farese AM, Cohen MV, Katz BP, et al. Filgrastim improves survival in lethally irradiated nonhuman primates. Radiat Res. 2013;179:89–100.
  • U.S. Food and Drug Administration. FDA approves neupogen for treatment of patients with radiation-induced myelosuppression following a radiological/nuclear incident; 2015. [cited 2015 Apr 17]. Available from: http://www.fda.gov/EmergencyPreparedness/Counterterrorism/MedicalCountermeasures/AboutMCMi/ucm443245.htm
  • Molineux G, Kinstler O, Briddell B, et al. A new form of filgrastim with sustained duration in vivo and enhanced ability to mobilize PBPC in both mice and humans. Exp Hematol. 1999;27:1724–1734.
  • Farese AM, Cohen MV, Stead RB, et al. Pegfilgrastim administered in an abbreviated schedule, significantly improved neutrophil recovery after high-dose radiation-induced myelosuppression in rhesus macaques. Radiat Res. 2012;178:403–413.
  • Chua HL, Plett PA, Sampson CH, et al. Survival efficacy of the PEGylated G-CSFs, Maxy-G34, and Neulasta in a mouse model of lethal H-ARS, and residual bone marrow damage in treated survivors. Health Phys. 2014;106:21–38.
  • Kiang JG, Zhai M, Liao PJ, et al. Pegylated G-CSF inhibits blood cell depletion, increases platelets, blocks splenomegaly, and improves survival after whole-body ionizing irradiation but not after irradiation combined with burn. Oxid Med Cell Longev. 2014;2014:481392.
  • Richter W, Weber L. Use of tri-substituted glycerol compounds for the treatment of radiation injuries. CA2668923C. 2015.
  • Basile LA, Ellefson D, Gluzman-Poltorak Z, et al. HemaMax, a recombinant human interleukin-12, is a potent mitigator of acute radiation injury in mice and non-human primates. PLoS One. 2012;7:e30434.
  • Gluzman-Poltorak Z, Mendonca SR, Vainstein V, et al. Randomized comparison of single dose of recombinant human IL-12 versus placebo for restoration of hematopoiesis and improved survival in rhesus monkeys exposed to lethal radiation. J Hematol Oncol. 2014;7:31.
  • Gluzman-Poltorak Z, Vainstein V, Basile LA. Recombinant interleukin-12, but not granulocyte-colony stimulating factor, improves survival in lethally irradiated nonhuman primates in the absence of supportive care: evidence for the development of a frontline radiation medical countermeasure. Am J Hematol. 2014;89:868–873.
  • Gluzman-Poltorak Z, Vainstein V, Basile LA. Association of hematological nadirs and survival in a nonhuman primate model of hematopoietic syndrome of acute radiation syndrome. Radiat Res. 2015;184:226–230.
  • Ellefson D, Galalaher T, Gluzman-Poltorak Z, et al. Mitigation of radiation combined injury (RCI) by interleukin-12. 14th Intl Cong Radiat Resh; 2011; Poland Warsaw.
  • Wipf P, Frantz MC. Targeted nitroxide agents. US9216976B2. 2015.
  • Crapo JD, Marcondes AMQ, Deeg HJ. Method for ameliorating radiation exposure effects with alpha-1 antitrypsin. US8980574B2. 2015.
  • Kantara C, Moya SM, Houchen CW, et al. Novel regenerative peptide TP508 mitigates radiation-induced gastrointestinal damage by activating stem cells and preserving crypt integrity. Lab Invest. 2015;95:1222–1233.
  • MacVittie TJ, Bennett AW, Farese AM, et al. The effect of radiation dose and variation in neupogen(R) initiation schedule on the mitigation of myelosuppression during the concomitant GI-ARS and H-ARS in a nonhuman primate model of high-dose exposure with marrow sparing. Health Phys. 2015;109:427–439.
  • Pejchal J, Sinkorova Z, Tichy A, et al. Attenuation of radiation-induced gastrointestinal damage by epidermal growth factor and bone marrow transplantation in mice. Int J Radiat Biol. 2015;91:703–714.
  • Deng W, Kimura Y, Gududuru V, et al. Mitigation of the hematopoietic and gastrointestinal acute radiation syndrome by octadecenyl thiophosphate, a small molecule mimic of lysophosphatidic acid. Radiat Res. 2015;183:465–475.
  • Fox BS, Stafford DC. Antibody therapy medium with local activity in the digestive tract. EP2488202B1. 2015.
  • Xiaojing W, Farley Y, Qinghong Z. Smad7 therapeutic applications. CN103501803B. 2015.
  • Seed TM. Radiation protectants: current status and future prospects. Health Phys. 2005;89:531–545.
  • Singh VK, Beattie LA, Seed TM. Vitamin E: tocopherols and tocotrienols as potential radiation countermeasures. J Radiat Res. 2013;54:973–988.
  • Epperly M, Greenberger J, Jiang J, et al. Radioprotective agents. US8883852B2. 2014.
  • Benner R, Khan NA, Carlton RM. Use of peptides for the control of radiation injury. CA2645550C. 2014.
  • Okunieff P, Zhang L. Fibroblast growth factor (FGF) analogs and uses thereof. EP2310035B1. 2015.
  • Wang CH, Chen CH, Chen JY, et al. Pharmaceutical compositions. US8648042B2. 2014.
  • Djang AHK. Methods for radiation protection. US8765193B2. 2014.
  • DiCarlo AL, Ramakrishnan N, Hatchett RJ. Radiation combined injury: overview of NIAID research. Health Phys. 2010;98:863–867.
  • Benjamin GC, McGeary M, McCutchen SR. Assessing medical preparedness to respond to a terrorist nuclear event: workshop report. Washington, DC: The National Academies Press; 2009.
  • Singh VK, Ducey EJ, Brown DS, et al. A review of radiation countermeasure work ongoing at the Armed Forces Radiobiology Research Institute. Int J Radiat Biol. 2012;88:296–310.
  • Elliott TB, Bolduc DL, Ledney GD, et al. Combined immunomodulator and antimicrobial therapy eliminates polymicrobial sepsis and modulates cytokine production in combined injured mice. Int J Radiat Biol. 2015;91:690–702.
  • Brook I, Elliott TB, Ledney GD, et al. Management of postirradiation infection: lessons learned from animal models. Mil Med. 2004;169:194–197.
  • Brook I, Ledney GD. Quinolone therapy in the management of infection after irradiation. Crit Rev Microbiol. 1992;18:235–246.
  • Ran XZ, Shi CM, Zheng HE, et al. Experimental research on the management of combined radiation-burn injury in China. Radiat Res. 2011;175:382–389.
  • Jacob A, Shah KG, Wu R, et al. Ghrelin as a novel therapy for radiation combined injury. Mol Med. 2010;16:137–143.
  • Rodgers KE, diZerega GS. Methods for treating combined radiation and thermal injury. JP5823486. 2015.
  • Denisenko PP, Sapronov NS, Tarasenko AA. Nitrostyrene derivatives with antimicrobial action. EP2468275B1. 2015.
  • Kels CG. Dispensing medical countermeasures: emergency use authorities and liability protections. Health Secur. 2015;13:139–151.
  • van Os R, Robinson S, Sheridan T, et al. Granulocyte-colony stimulating factor impedes recovery from damage caused by cytotoxic agents through increased differentiation at the expense of self-renewal. Stem Cells. 2000;18:120–127.
  • Adachi K, Suzuki M, Sugimoto T, et al. Effects of granulocyte colony-stimulating factor (G-CSF) on bleomycin-induced lung injury of varying severity. Toxicol Pathol. 2003;31:665–673.
  • Inokuchi R, Manabe H, Ohta F, et al. Granulocyte colony-stimulating factor-producing lung cancer and acute respiratory distress syndrome. Clin Respir J. 2015;9:250–252.
  • International Atomic Energy Agency. The radiological accident in gilan; 2002. [cited 2014 Feb 10]. Available from: http://www-pub.iaea.org/books/IAEABooks/6284/The-Radiological-Accident-in-Gilan
  • Nightengale SL, Prasher JM, Simonson S. Emergency use authorization (EUA) to enable use of needed products in civilian and military emergencies, United States. Emerging Infect Dis. 2007;13:1046–1055.
  • Gronvall G. Biodefense countermeasures: the impact of title IV of the US Pandemic and All-Hazards Preparedness Act. Emerg Health Threats J. 2008;1:e3.
  • Aebersold P. FDA experience with medical countermeasures under the Animal Rule. Adv Prev Med. 2012;2012:507571.
  • Wang J, Shao L, Hendrickson HP, et al. Total body irradiation in the “hematopoietic” dose range induces substantial intestinal injury in non-human primates. Radiat Res. 2015;184:545–553.
  • Rotolo JA, Kolesnick R, Fuks Z. Timing of lethality from gastrointestinal syndrome in mice revisited. Int J Radiat Oncol Biol Phys. 2009;73:6–8.
  • Rotolo JA, Mesicek J, Maj J, et al. Regulation of ceramide synthase-mediated crypt epithelium apoptosis by DNA damage repair enzymes. Cancer Res. 2010;70:957–967.
  • Rotolo J, Stancevic B, Zhang J, et al. Anti-ceramide antibody prevents the radiation gastrointestinal syndrome in mice. J Clin Invest. 2012;122:1786–1790.
  • Krivokrysenko VI, Shakhov AN, Singh VK, et al. Identification of granulocyte colony-stimulating factor and interleukin-6 as candidate biomarkers of CBLB502 efficacy as a medical radiation countermeasure. J Pharmacol Exp Ther. 2012;343:497–508.
  • Krivokrysenko VI, Toshkov IA, Gleiberman AS, et al. The Toll-like receptor 5 agonist Entolimod mitigates lethal acute radiation syndrome in non-human primates. PLoS One. 2015;10:e0135388.
  • Singh VK, Kulkarni S, Fatanmi OO, et al. Radioprotective efficacy of gamma-tocotrienol in nonhuman primates. Radiat Res. 2016;185:285–298.
  • Kulkarni S, Singh PK, Ghosh SP, et al. Granulocyte colony-stimulating factor antibody abrogates radioprotective efficacy of gamma-tocotrienol, a promising radiation countermeasure. Cytokine. 2013;62:278–285.
  • Singh VK, Hauer-Jensen M. Gamma-tocotrienol as a promising countermeasure for acute radiation syndrome: current status. Int J Mol Sci. 2016;17:e663.