DEVELOPMENT OF A NOVEL GASTROINTESTINAL RADIOMITIGATOR

这个子项目是许多利用资源的研究子项目之一 由NIH/NCRR资助的中心拨款提供。子项目的主要支持 而子项目的主要调查员可能是由其他来源提供的， 包括其它NIH来源。 列出的子项目总成本可能 代表子项目使用的中心基础设施的估计数量， 而不是由NCRR赠款提供给子项目或子项目工作人员的直接资金。 人们意外或有目的地暴露于高水平辐射会造成严重的直接风险和潜在的长期健康风险。目前还没有FDA批准的在辐射损伤后24- 48小时有效的抗辐射剂。因此，有一个关键的未满足的医疗需要，以保护人民免受这些有害影响的意外辐射。我们在小鼠模型中建立了十八烯基硫代磷酸盐（OTP），通过单次皮下注射致死水平的γ-照射后26小时给药，可增加隐窝计数和存活率，剂量修正系数为1.2。本申请的总体目标是将OTP开发为胃肠放射性激动剂，用于暴露于致命电离辐射的人类受试者，所述电离辐射是核事故或恐怖袭击的结果。本项目将为十八烯基硫代磷酸盐作为胃肠道放射性激动剂用于暴露于致命电离辐射的人类受试者的“药物主文件”提供非人灵长类动物安全性和有效性数据，从而能够根据FDA动物规则提交IND申请。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. Accidental or purposeful exposure of people to high levels of radiation poses a serious immediate risk and potential long-term health risk. No FDA approved radiomitigant effective 24-48h after radiation injury is available today. Thus, there is a critical unmet medical need to shield the population from these harmful effects of unintended radiation. We established in murine models that octadecenyl thiophosphate (OTP) administered 26 h after lethal levels of gamma-irradiation by a single subcutaneous injection increases crypt counts and survival with a dose modification factor of 1.2. The overall objective of this application is to develop OTP as a gastrointestinal radiomitigator for use in human subjects exposed to lethal ionizing radiation either as a result of nuclear accident or terrorist attack. This project will provide non-human primate safety and efficacy data for a "drug master file" for octadecenyl thiophosphate as a gastrointestinal radiomitigator for use in human subjects exposed to lethal ionizing radiation enabling the filing of an IND application based on the Animal Rule of the FDA.