PRECLINICAL DEVELOPMENT OF A GI RADIATION COUNTERMEASURE

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 人们意外或有意地暴露在高水平的辐射中，构成了严重的直接风险和潜在的长期健康风险。今天没有FDA批准的在辐射损伤后24-48小时有效的放射增强剂。因此，有一个关键的未得到满足的医疗需求，即保护人们免受这些意外辐射的有害影响。我们在小鼠模型中建立了十八烯基硫代磷酸酯(OTP)在致死水平的伽马照射后26小时单次皮下注射增加隐窝数量和存活率的模型，剂量修正系数为1.2。这一应用的总体目标是开发OTP作为胃肠道放射增强剂，用于因核事故或恐怖袭击而暴露于致命电离辐射的人体受试者。该项目将提供非人类灵长类动物的安全性和有效性数据，用于将十八烯基硫代磷酸作为胃肠道放射增强剂，用于暴露在致命性电离辐射下的人体受试者，使其能够根据FDA的动物规则提交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.