Chua, Hui LinPlett, P. ArturSampson, Carol H.Katz, Barry P.Carnathan, Gilbert W.MacVittie, Thomas J.Lenden, KeithOrschell, Christie M.2016-03-242016-03-242014-01Chua, H. L., Plett, P. A., Sampson, C. H., Katz, B. P., Carnathan, G. W., MacVittie, T. J., … Orschell, C. M. (2014). 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 Physics, 106(1), 10.1097/HP.0b013e3182a4df10. http://doi.org/10.1097/HP.0b013e3182a4df101538-5159https://hdl.handle.net/1805/9011In an effort to expand the worldwide pool of available medical countermeasures (MCM) against radiation, the PEGylated G-CSF (PEG-G-CSF) molecules Neulasta and Maxy-G34, a novel PEG-G-CSF designed for increased half-life and enhanced activity compared to Neulasta, were examined in a murine model of the Hematopoietic Syndrome of the Acute Radiation Syndrome (H-ARS), along with the lead MCM for licensure and stockpiling, G-CSF. Both PEG-G-CSFs were shown to retain significant survival efficacy when administered as a single dose 24 h post-exposure, compared to the 16 daily doses of G-CSF required for survival efficacy. Furthermore, 0.1 mg kg of either PEG-G-CSF affected survival of lethally-irradiated mice that was similar to a 10-fold higher dose. The one dose/low dose administration schedules are attractive attributes of radiation MCM given the logistical challenges of medical care in a mass casualty event. Maxy-G34-treated mice that survived H-ARS were examined for residual bone marrow damage (RBMD) up to 9 mo post-exposure. Despite differences in Sca-1 expression and cell cycle position in some hematopoietic progenitor phenotypes, Maxy-G34-treated mice exhibited the same degree of hematopoietic stem cell (HSC) insufficiency as vehicle-treated H-ARS survivors in competitive transplantation assays of 150 purified Sca-1+cKit+lin-CD150+cells. These data suggest that Maxy-G34, at the dose, schedule, and time frame examined, did not mitigate RBMD but significantly increased survival from H-ARS at one-tenth the dose previously tested, providing strong support for advanced development of Maxy-G34, as well as Neulasta, as MCM against radiation.en-USPublisher PolicyAcute Radiation Syndromedrug therapyBone Marrowdrug effectsradiation effectsGranulocyte Colony-Stimulating FactorpharmacologyPolyethylene GlycolsArticle