The peripheral blood contains only a small fraction of the total number of lymphocytes in the body. Therefore, a thorough understanding of T-cell dynamics, including SIV/SHIV/HIV-mediated T cell depletion, T-cell trafficking and immune reconstitution following combination antiretroviral therapy (cART), requires a direct whole body in vivo visualization of lymphoid tissues. Although in the past decades immunologists have attempted to address some of these questions using optical imaging technologies, the latter are unable to generate quantitative information from deep tissues, due to attenuation and scattering of low energy photons, hence limiting their use to rodent models. NIAID scientists have demonstrated the feasibility of CD4 pool in vivo imaging in non-human primates using intact or fragmented anti-CD4 monoclonal antibodies radiolabeled with single photon gamma or positron emitters, and Single Photon Emission Computed Tomography (SPECT) or Positron Emission Tomography (PET) cameras, respectively. Although both SPECT and PET document differences in CD4 pools of lymphoid tissues between healthy and SIV/SHIV CD4 depleted animals, PET’s higher sensitivity, resolution and unique quantitative imaging capability allows the quantification of the absolute number of CD4 receptors (per unit volume of tissue), in vivo, as recently reported. Ibalizumab is an FDA-approved recombinant humanized IgG4 mouse anti-human-CD4 monoclonal antibody administered intravenously (IV) for the treatment of multi-drug resistant HIV infection. The NIAID team has successfully radiolabeled Ibalizumab via a deferoxamine conjugate with Zirconium-89 (89Zr), a positron emitter with a 78h half-life that allows serial imaging over at least 1 week with the additional benefit of commercial distribution and ease of patient scheduling as compared to other positron emitters such as 64Cu (12.7h half-life). They have developed and validated the methods and quality control for conjugating Ibalizumab with deferoxamine (DF-Ibalizumab) and radiolabeling with 89Zr to produce 89Zr-DF-Ibalizumab using established methods and have recently produced PET images of the whole-body CD4 pool in healthy and SIV CD4 depleted macaques with quality similar to those generated with previously developed PET anti-CD4 probes in the NIAID program. This proof-of-concept study aims to establish the safety and capability of a GMP developed 89Zr-DF-Ibalizumab to visualize the CD4 pool in humans through a single-site, open-label, non-randomized, phase 1 trial.