Significant Reduction of Total-Body Irradiation-Induced Death in Mice Treated with PrC-210 24 Hours Postirradiation.

Abstract

The search for radiation countermeasures that can serve as: i. a pre-exposure agent to protect against subsequent irradiation, and/or ii. a post-exposure agent to mitigate the development of Acute Radiation Syndrome after radiation exposure, remains a prominent goal of the U.S. Government. This study was undertaken to determine whether PrC-210, when administered once, 24 h postirradiation, would provide a survival benefit and would mitigate Acute Radiation Syndrome in mice that had received an otherwise 95-100% lethal radiation dose. Our results show that a single intraperitoneal dose of PrC-210 (0.3-0.4 MTD, 151-201 ug/gm body weight) administered 24 h postirradiation, conferred: i. a 45% survival advantage (P = 0.002) in outbred ICR mice and a 25% survival advantage (P = 0.037) in inbred C57Bl/6 mice, ii. a significant increase in body weight in surviving mice (P = 0.012), iii. a discernible protection of intestinal structure by MRI imaging of live mice, iv. visibly denser jejunal villi and surface epithelium and v. visible bone marrow population in PrC-210-treated mice versus saline controls. The ability of PrC-210 to suppress 100% of radiation-induced death when administered minutes before irradiation, or roughly half of this effect (45%) when administered 24 h postirradiation is noteworthy. Determining the multiple paths by which PrC-210 protection is conferred is a process; the results in this report showing protection of two of the major systems central to Acute Radiation Syndrome damage, is a good first step. This was the first study of PrC-210 administered postirradiation; it conferred substantial survival benefit and suppression of Acute Radiation Syndrome. This outcome supports the continued development of PrC-210 to protect humans exposed to ionizing radiation.