Development of Selective Nanoporous Sorbents for Radionuclide Decorporation

用于放射性核素修饰的选择性纳米孔吸附剂的开发

• 批准号: 7267893
• 负责人: CHARLES TIMCHALK
• 金额: $ 59.97万
• 依托单位: BATTELLE PACIFIC NORTHWEST LABORATORIES
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-09-10 至 2009-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7267893
• 关键词: clinical research; human; radionuclides

DESCRIPTION (provided by applicant): The Department of Health and Human Services has charged NIH with the mission of developing new medical countermeasures against radiological or nuclear attacks. As part of Project Bioshield, NIH has established a research goal of developing novel radionuclide chelation and decorporation agents for protection against terrorist attacks that involve radiological dispersion devices (RDD), (e.g. dirty bombs) or nuclear detonations. This project will focus on new product development and validation to minimize systemic exposure to radionuclides through novel chelating materials. We propose to develop and validate in animal (in vivo) and human (in vitro) systems new nano-engineered solid sorbants, which have advantages over their liquid counterparts in minimizing the absorption of harmful agents into the body and thereby reducing the kidney burden for clearing the radionuclide-bound complex. At the Pacific Northwest National Laboratory (PNNL), a new class of nano-engineered sorbants, self-assembled monolayer on mesoporous supports (SAMMS) materials, has been developed to facilitate the cleanup of radionuclides from complex waste found at the DCL sites. Created by installation of well-designed organic moieties onto the highly ordered mesoporous silica, the SAMMS materials have been demonstrated to be highly effective chelators for plutonium, neptunium, uranium, americium, radiolodide, cesium and cobalt, all of which can be normally found in nuclear bombs and RDD. The current proposal focuses on extending the application of SAMMS from their proven utility in environmental clean-up to their utility for radionuclide decorporation in humans. The overall goal of this project is to develop and validate SAMMS materials, and evaluate their toxicity (if any) for use in decorporation of humans following acute exposures to radionuclides. The approach focuses on two specific applications: (1) to chelate radionuclides within the gastrointestinal tract in order to limit systemic absorption of ingested materials and (2) to chelate radionuclides in blood that have been absorbed systemically from all routes of exposure (oral, dermal and inhalation). It is anticipated that the proposed experiments will demonstrate that SAMMS can outperform current FDA-approved chelation therapies by having higher binding affinity and selectivity for the target radionuclides among other non-target species, larger sorption capacity and rapid sorption rate, favorable benefit to risk ratio, and will be available at low costs. Once we have established increased efficacy and safety of SAMMS for radionuclide decorporation, candidate SAMMS will be advanced towards FDA licensure, with a goal of accelerated deployment to protect the public during a nuclear incident that may cause a public health emergency affecting national security.

描述（由申请人提供）：美国卫生与公众服务部已委托 NIH 负责开发针对放射性或核攻击的新医疗对策。作为生物盾计划的一部分，美国国立卫生研究院制定了开发新型放射性核素螯合剂和脱核剂的研究目标，以防止涉及放射性分散装置（RDD）（例如脏弹）或核爆炸的恐怖袭击。该项目将重点关注新产品的开发和验证，以通过新型螯合材料最大限度地减少放射性核素的全身暴露。我们建议在动物（体内）和人类（体外）系统中开发和验证新型纳米工程固体吸附剂，与液体吸附剂相比，它在最大限度地减少有害物质吸收到体内方面具有优势，从而减轻肾脏负担清除放射性核素结合复合物。太平洋西北国家实验室 (PNNL) 开发了一种新型纳米工程吸附剂，即介孔支撑材料上的自组装单层 (SAMMS)，以促进 DCL 站点发现的复杂废物中放射性核素的清理。 SAMMS 材料是通过将精心设计的有机部分安装到高度有序的介孔二氧化硅上而创建的，已被证明是钚、镎、铀、镅、放射性碘化物、铯和钴的高效螯合剂，所有这些元素通常都可以在核弹和RDD。目前的提案侧重于将 SAMMS 的应用范围从其在环境清理中经过验证的实用性扩展到其在人类放射性核素去除中的实用性。该项目的总体目标是开发和验证 SAMMS 材料，并评估其毒性（如果有的话），用于在急性暴露于放射性核素后对人体进行解剖。该方法侧重于两个具体应用：(1) 螯合胃肠道内的放射性核素，以限制摄入物质的全身吸收；(2) 螯合血液中从所有暴露途径（口腔、皮肤）吸收的放射性核素。和吸入）。预计所提出的实验将证明 SAMMS 可以优于目前 FDA 批准的螯合疗法，因为它对其他非目标物质中的目标放射性核素具有更高的结合亲和力和选择性，更大的吸附能力和快速的吸附速率，有利的效益风险比，并且将以低成本提供。一旦我们确定了 SAMMS 在放射性核素修饰方面的有效性和安全性有所提高，候选 SAMMS 将获得 FDA 许可，目标是加速部署，以在可能导致影响国家安全的公共卫生紧急情况的核事件期间保护公众。