PET CONTRAST AGENT FOR INTERROGATING IMMUNODEFICIENCY VIRUS INFECTIONS

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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. 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 are proposing 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.