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）：卫生与公共服务部负责NIH的使命，要求开发针对放射学或核攻击的新医疗对策。作为Bioshield项目的一部分，NIH建立了一个研究目标，即开发新型的放射性核素螯合和装饰剂，以防止涉及放射线分散装置（RDD）的恐怖袭击（例如，肮脏的炸弹）或核爆炸。该项目将着重于新产品开发和验证，以通过新型的螯合材料最大程度地减少系统性暴露于放射性核素。我们建议在动物（体内）和人类（体外）系统中开发和验证新的纳米工程固体扫描剂，它们比其液体具有优势，可以最大程度地减少对体内的有害剂的吸收，从而减少肾脏负担减轻肾脏负担，从而清除了放射线核酸酯结合的核心结合的复合物。在Pacific Northwest国家实验室（PNNL）中，已经开发了一种新的纳米工程吸附剂，自组装单层介孔支架（SAMMS）材料已开发出来，以促进在DCL站点发现的复杂废物中从复杂废物中清理radionuclides。通过在高度有序的介孔二氧化硅上安装精心设计的有机部分，SAMMS材料已被证明是用于plut骨，Neptnium，Neptnium，Neptunium，Americium，randiolodide，cesium和Cobalt的高效螯合剂，通常在核Bombs和Rdd中都可以找到所有这些。当前的提案着重于将SAMM从其在环境清理中的验证效用扩展到其对人类放射性核素装饰的效用。该项目的总体目标是开发和验证SAMMS材料，并评估其急性暴露于放射性核素后用于装饰人类的毒性（如果有）。该方法侧重于两个特定的应用：（1）胃肠道内的螯合物放射性核素，以限制摄入的材料的全身吸收，（2）到血液中的螯合物放射性核素，这些核素已从所有暴露途径（口腔，皮肤，皮肤和吸入）中系统地吸收。可以预计，提出的实验将证明，SAMM可以通过具有较高的结合亲和力和对目标放射性核素的选择性较高，在其他非目标物种中具有较高的结合亲和力和选择性，较大的吸附能力和快速吸附率，有利的风险比率，并以低成本可用。一旦我们确定了SAMMS对放射性核素装饰的疗效和安全性，候选人SAMMS将提高到FDA许可方面，其目的是加速部署以保护公众在核事件中可能导致公共卫生紧急情况，这可能会对国家安全产生影响。