Premium
Radioprotective and Radiomitigative Efficacy of Flt3 Ligand in a Murine Model of Acute Radiation Injury.
Author(s) -
Thomas Lawrence J.,
Boyer James M.,
Round Sarah M.,
Naylor Sarah R.,
Forsberg Eric M.,
Borrelli Kathleen M.,
Pilsmaker Catherine D.,
Gergel Lauren E.,
Marsh Henry C.,
Keler Tibor
Publication year - 2013
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.27.1_supplement.1181.3
Subject(s) - medicine , acute radiation syndrome , haematopoiesis , irradiation , total body irradiation , pharmacology , progenitor cell , whole body irradiation , stem cell , bone marrow , biology , chemotherapy , physics , nuclear physics , genetics , cyclophosphamide
Radiation exposure can occur either intentionally or unintentionally and few drugs have been shown to be effective in mitigating or treating the damaging effects of radiation. Flt3 Ligand (Flt3L, fms‐like tyrosine kinase 3 ligand, CDX‐301) is a hematopoietic cytokine which stimulates the proliferation and differentiation of various blood cell progenitors. We sought to determine the efficacy of Flt3L monotherapy on survival at 30 days following total body irradiation at a LD50 level (LD50/30). C57BL/6 mice were exposed to a single total body gamma radiation dose of approximately 776 cGy from a 137 Cs source. Flt3L was administered subcutaneously for 10 sequential daily 25 μg doses beginning 24 hours before irradiation, or 4 or 24 hours after irradiation. Mice were observed twice daily to monitor for morbidity and mortality for 30 days post‐irradiation and animals were euthanized based on criteria approved by the IACUC. As anticipated, 45% of untreated animals did not survive to day 30, where no animals treated with Flt3L s.c. beginning 24 hours before irradiation did not survive to day 30 (p≤0.0001). If Flt3L treatment was started 4 hours after irradiation, only 10% of mice did not survive at day 30 (p≤0.0107) and if treatment was started 24 hours after irradiation 22% did not survive to day 30 (p≤0.0898). In conclusion, data suggest that Flt3L monotherapy can serve as an effective radioprotectant and radiomitigant.