First-in-human total-body PET imaging of HIV with 89Zr-VRC01 on the EXPLORER

545 Introduction: Despite the striking success of antiretroviral therapy (ART) in HIV+ patients, HIV remains a serious global threat. HIV persists in anatomical reservoirs despite the use of suppressive combination ART, and virus rebounds upon cessation of therapy. These reservoirs largely reside in tissue compartments that are inaccessible to routine sampling.[1] A major hurdle to achieve HIV eradication, an ultimate goal for many in the HIV community, is the limited ability to fully identify and characterize the whole-body viral burden in ART suppressed individuals. We have developed 89Zr-VRC01, a positron-labeled broadly neutralizing monoclonal antibody that targets the CD4 binding sites of the HIV-1 external envelope protein (gp120), as an imaging agent for HIV reservoirs and shown uptake values in tissues known to harbor HIV (lymph nodes, bone marrow and testes) were significantly higher in HIV-infected participants than in uninfected controls. Remarkably, we observed higher 89Zr-VRC01 uptake in ART-suppressed HIV patients compared to uninfected controls. The objective of this work was to evaluate total-body PET of 89Zr-VRC01 antibody and compare the images to PET/MR images taken the same day on a conventional PET/MR scanner, and to characterize the whole-body viral load in patients on and off ART using the uEXPLORER total-body PET/CT scanner. Methods: VRC01 was modified with p-benzyl-isothiocyanate-deferoxamine and radiolabeled with zirconium-89 (3D Imaging, Little Rock AR). 89Zr-VRC01 was produced at the UCSF Radiopharmaceutical facility and it was released for patient administration following quality control (QC) testing. 89Zr-VRC01 was intravenously administered (26.6-33.3 MBq, 1-2 mg of antibody mass). PET/MR (GE SIGNA) at UCSF and total-body PET/CT at UC Davis (uEXPLORER) were performed serially 48-76h post injection. Imaging was performed on two male HIV-infected participants including one on chronic suppressive ART for >10 years and one with low level viremia not currently on therapy. Results: 89Zr-VRC01 was obtained with radiochemical purity of 99% and all the batches successfully passed all the QC tests. Participants were injected 2 and 3 days prior to PET-MR imaging at UCSF, followed by immediate transport and EXPLORER imaging at UC Davis on the same day. EXPLORER imaging was performed within 3 hours of PET-MR. Figure 1 shows coronal 3-dimensional projection of PET signal on each scanner 72h (ART suppressed patient) and 48h (low-level viremic patient) after injection. The total acquisition time for PET-MR was 48 min (8 min per bed position, 6 positions) versus 20 min for the EXPLORER scan. Analysis of the images (SUVmax blood pool adjusted) demonstrated higher uptake in the iliac marrow, inguinal and axillary lymph nodes for the viremic patient versus the ART suppressed patient, consistent with our previous studies. Uptake in the spinal marrow is evident in both patients (Figure 1). Conclusions: This study represents the first-in-human 89Zr-radiolabeled antibody total-body EXPLORER immunoPET image. As seen in Figure 1 the total-body EXPLORER images, acquired in less than half the time, are superior to the PET MR images. Utilization of total-body imaging demonstrates the potential to inform on whole-body anatomical localization and burden of persistent HIV infection. Acknowledgments: This study was supported by amfAR 109301-59-RGRL and R01CA206187. The authors thank the Vaccine Research Center at NIH for the GMP grade VRC01 antibody. References: [1] Kulpa DA, Chomont N (2015) J Virus Erad 1:59-66.