PRECLINICAL DEVELOPMENT OF A GI RADIATION COUNTERMEASURE

这个子项目是许多研究子项目中的一个 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得了主要资金， 因此可以在其他CRISP条目中表示。所列机构为 研究中心，而研究中心不一定是研究者所在的机构。 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. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. 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.