IN VIVO LOCALIZATION OF ANTHRAX TOXINS BY MAGNETIC RESONANCE IMAGING

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。 引起疾病的细菌有各种各样的创造性方法，它们用来入侵宿主并繁殖。 细菌的武器库中比较成功的一种是毒素，细菌分泌毒素到周围环境中杀死周围环境中的宿主细胞，从而允许更深入地渗透到组织中，或者使宿主的防御反应丧失能力。 对于这些产生毒素的细菌，单独的抗生素治疗是不够的，因为毒素造成的损害通常与致命性直接相关。 筛选抗毒素药物的传统方法通常是在啮齿动物模型中进行存活研究，这是费力的并且仅提供有限的信息。 目前的研究开发了一种新的方法，使用靶向磁共振成像技术直接可视化毒素在体内的定位以及潜在抗毒素治疗的后续效果。 从炭疽芽孢杆菌（炭疽）的毒素组分获得的初步数据表明，在炎症条件下，毒素敏感小鼠的肾脏和肝脏定位。 数据采集快速，同时进行生理监测。 继续开发适当的成像探针将提高灵敏度和选择性。 该方法应适用于各种毒素，并将有助于更快地开发，筛选和抗毒素药物的临床前测试。

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. Bacteria that cause diseases have a variety of creative methods which they use to invade a host and propagate. One of the more successful in their arsenal is toxins which the bacteria secrete into the milieu to kill host cells in the immediate environment, thereby permitting deeper penetration into tissues, or perhaps to incapacitate host defense responses. For these toxin-producing bacteria, antibiotic treatment alone is insufficient because the damage done by the toxins is often directly linked to lethality. Traditional methods to screen for anti-toxin drugs are usually survival studies in rodent models which are laborious and provide only limited information. The current study develops a new approach using targeted magnetic resonance imaging techniques to directly visualize where a toxin localizes in vivo and subsequent effects of potential anti-toxin therapeutics. Preliminary data obtained with a toxin component from Bacillus anthracis (anthrax) demonstrate renal and liver localization in toxin-sensitive mice under inflammatory conditions. Data acquisition is rapid with concomitant physiological monitoring. Continued development of appropriate imaging probes will improve sensitivity and selectivity. The methodology should be applicable to a variety of toxins and will contribute to more rapid development, screening, and pre-clinical testing of anti-toxin drugs.