PET CONTRAST AGENT FOR INTERROGATING IMMUNODEFICIENCY VIRUS INFECTIONS

用于检查免疫缺陷病毒感染的宠物造影剂

• 批准号: 8357519
• 负责人: Eric Hunter
• 金额: $ 7.43万
• 依托单位: EMORY UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-08-01 至 2012-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8357519
• 关键词: Acquired Immunodeficiency Syndrome; Affinity; Antiviral Agents; Biological Models; Cell Culture Techniques; Cells; Contrast Media; Detection; Development; Diagnostic; Funding; Grant; HIV Envelope Protein gp120; HIV Infections; Half-Life; Human; Image; Immunoglobulin Fragments; Immunologic Deficiency Syndromes; Infection; Infection prevention; Kinetics; Life; Ligands; Macaca; Macaca mulatta; Modeling; National Center for Research Resources; Positron-Emission Tomography; Primates; Principal Investigator; Radiolabeled; Research; Research Infrastructure; Resources; SIV; Scanning; Source; Specificity; Time; United States National Institutes of Health; Vaccines; Virus Diseases; cost; in vivo; radiotracer; recombinant peptide; simian immunodeficiency virus gp120

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.

该子项目是利用资源的众多研究子项目之一 由 NIH/NCRR 资助的中心拨款提供。子项目的主要支持 并且子项目的首席研究员可能是由其他来源提供的， 包括其他 NIH 来源。 子项目可能列出的总成本 代表子项目使用的中心基础设施的估计数量， NCRR 赠款不直接向子项目或子项目工作人员提供资金。 目前，还没有可以评估活体受试者体内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取有关感染的时间过程信息。这对于评估疫苗预防感染或破坏体内受感染细胞的能力，以及对于表征新抗病毒药物的功效和动力学非常有用。 在这笔资助中，我们建议使用恒河猴的猿猴免疫缺陷病毒（SIV）感染作为我们的模型系统来开发正电子发射断层扫描（PET）造影剂。 该模型系统目前能够最准确地表征人类艾滋病毒感染和获得性免疫缺陷综合症（艾滋病）。 我们的具体目标是： AIM 1) 在细胞培养模型中开发针对 SIV gp120 的高亲和力配体。 抗体片段、肽和重组 CD4 将被优化和比较，以找到 gp120 的最高亲和力和特异性配体。目的 2) 使用放射性标记探针对活体猕猴 SIV 感染过程中的感染细胞进行成像。 放射性标记探针由高亲和力配体和 64Cu（半衰期 12.7 小时）组成，这是一种与 PET 成像兼容的放射性标记，将在感染过程中的不同日期注射到受感染的猕猴体内并进行成像，以确定最短扫描时间和范围可以进行扫描以最大程度地检测猕猴内的受感染细胞。