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WHOLE-BODY PET IMAGING OF THE HIV RESERVOIR USING RADIOLABELED VRC01
Timothy J. Henrich1, Denis Beckford-Vera1, Enrique Martinez-Ortiz1, Maya Aslam1, Cassandra Thanh1, Shreya Kumar1, I-Wei Katherine Wu1, Rebecca Hoh1, Robert Flavell1University of California San Francisco, San Francisco, CA, USA,2Université de Montréal, Montreal, QC, Canada,3Vaccine Research Center, NIAID, Bethesda, MD, USA
HIV largely resides in anatomical regions that are inaccessible to routine sampling, and non-invasive methods to understand the tissue-wide burden of HIV are urgently needed. We report on the first-in-human PET-magnetic resonance (MR) imaging studies of HIV infection using a radiolabeled HIV Env-specific mAb, 89Zr-VRC01.
PET-MR imaging using 89Zr-VRC01 (t1/2=73h) was performed on 5 viremic participants (plasma HIV-1 RNA ranging from 3,459 to 789,705 c/mL), 4 ART-suppressed participants (duration of ART ranging from 3.5 to 280 months), and 5 uninfected controls. PET-MR imaging was performed 2h, 6h, 24h, 72h (day 3), and, in a subgroup of 6 participants, 132h (day 6) following a single 1 mCi injection of 89Zr-VRC01. Radiotracer maximum and mean standard uptake values (SUVmax, SUVmean) adjusted for blood pool background signal were quantified for various lymphoid and other anatomical regions of interest.
Adjusted 89Zr-VRC01 SUVs were significantly higher in inguinal and axillary lymph nodes, nasal-associated lymphoid tissue (NALT), and bone marrow in viremic participants compared with uninfected controls (all P<0.05). SUVmax/mean (NALT, bone marrow) and SUVmean (inguinal lymph node) were significantly higher in ART-suppressed individuals compared with uninfected controls, and generally lower than in viremic participants. The greatest differences between SUVs in HIV-infected and control participants were observed 72h after tracer injection, although differences in tracer uptake in inguinal lymph node tissue were observed up to 6 days following tracer injection (Figure). 89Zr-VRC01 inguinal lymph node SUVmax in viremic and ART-suppressed participants positively correlated with the frequency of p24 expressing cells measured by flow cytometry in fine needle aspirates (p=0.017). 89Zr-VRC01 tracer uptake in lymphoid tissues was lower in participants who were on suppressive ART for longer periods of time.
HIV envelope-specific PET imaging was able to detect differences between HIV-infected individuals, including those on suppressive ART, and uninfected participants. Importantly, PET tracer uptake correlated with measures of HIV protein expression in tissue. These data suggest that PET imaging of HIV-infected cells has the potential to localize and quantify multiple anatomical HIV reservoirs in a wide range of HIV persistence and curative studies.