PET CONTRAST AGENT FOR INTERROGATING IMMUNODEFICIENCY VIRUS INFECTIONS

这个子项目是许多利用资源的研究子项目之一 由NIH/NCRR资助的中心拨款提供。子项目的主要支持 而子项目的主要调查员可能是由其他来源提供的， 包括其它NIH来源。 列出的子项目总成本可能 代表子项目使用的中心基础设施的估计数量， 而不是由NCRR赠款提供给子项目或子项目工作人员的直接资金。 目前，还没有允许评估活体受试者内的免疫缺陷病毒感染的体内诊断剂或造影剂。 这种诊断将识别体内受感染的细胞，并提供一种非侵入性的方式来获得有关感染的时间过程信息。它对于评估疫苗预防感染或破坏体内受感染细胞的能力以及用于表征新抗病毒剂的功效和动力学将是非常宝贵的。 在这项研究中，我们提出了一种正电子发射断层扫描（PET）造影剂的发展使用猴免疫缺陷病毒（SIV）感染的恒河猴作为我们的模型系统。 该模型系统目前产生的艾滋病毒感染和获得性免疫缺陷综合征（艾滋病）在人类中的最准确的表示。 我们的具体目标是：目的1）在细胞培养模型中开发抗SIV gp 120的高亲和力配体。 将优化和比较抗体片段、肽和重组CD 4，以找到对gp 120的最高亲和力和特异性配体。目的2）用放射性标记探针对SIV感染猕猴的细胞进行成像。 将在感染过程中的不同日期将由高亲和力配体和64 Cu（12.7小时半衰期）（一种与PET成像相容的放射性标记）组成的放射性标记探针注射到感染的猕猴中，并进行成像以确定最小扫描时间和扫描程度，以最大限度地检测猕猴中的感染细胞。

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. Currently, there is no in-vivo diagnostic or contrast agent that allows the assessment of an immunodeficiency virus infection within a living subject. Such a diagnostic would identify infected cells within the body, and provide a non-invasive way of obtaining time-course information about the infection. It will be invaluable for assessing the ability of a vaccine to prevent infection or destroy infected cells within the body, as well as being useful for characterizing the efficacy and kinetics of new antiviral agents. In this grant, we propose the development of a positron emission tomography (PET) contrast agent using the simian immunodeficiency virus (SIV) infection of rhesus macaques as our model system. This model system currently yields the most accurate representation of an HIV infection and acquired immunodeficiency syndrome (AIDS) in humans. Our specific aims are: AIM 1) Develop a high affinity ligand against SIV gp120 in a cell culture model. Antibody fragments, peptides, and recombinant CD4 will be optimized and compared in order to find the highest affinity and specificity ligand for gp120. AIM 2) Image infected cells during time course of a SIV infection in live macaques using radiolabeled probe. Radiolabeled probes, composed of a high affinity ligand and 64Cu (12.7 hr half life), a radiolabel compatible with PET imaging, will be injected into infected macaques on different days during the time course of the infection and imaged to determine minimum scan time and extent of scan that can be performed to maximize our detection of infected cells within the macaques.