PRECLINICAL DEVELOPMENT OF A GI RADIATION COUNTERMEASURE

这个子项目是利用资源的许多研究子项目之一。 由NIH/NCRR资助的中心拨款提供。对子项目的主要支持 子项目的首席调查员可能是由其他来源提供的， 包括美国国立卫生研究院的其他来源。为子项目列出的总成本可能 表示该子项目使用的中心基础设施的估计数量， 不是由NCRR赠款提供给次级项目或次级项目工作人员的直接资金。 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. 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.