Whole-body PET imaging of SIV using anti-Env probes fails to reveal regions of specific uptake in rhesus macaques

Abstract

AbstractFollowing the initial reports demonstrating the feasibility of immunoPET imaging of SIV using anti-Env monoclonal antibodies in non-human primates, replication efforts of the imaging system in HIV-infected individuals have yielded conflicting results. Herein, we used89Zr-7D3 and89Zr- ITS103.01LS-F(ab’)2, two anti-gp120 antibodies for immunoPET imaging of SIV in n=20 rhesus macaques. Despite their demonstrated nanomolar affinity and strong binding specificity to SIV gp120 cell lines, we observed no discernible differences in their binding in primary cells, tissue sections of secondary lymphoid organs,in-vivoprobe uptake between SIVmac-infected and uninfected macaques, orex-vivovalidation necropsies. While the probes remained stablein-vivo, only89Zr-ITS103.01LS-F(ab’)2in chronic plasma retained its binding specificity to SIV gp120, with89Zr-7D3 experiencing a >97% reduction in binding to gp120 due to competition from endogenous antibodies at the 7D3 binding site. The overall absence of specific uptake suggests inadequate binding potential (ligand affinity x target molarity) for these probes to effectively image SIV or HIVin-vivo, warranting further investigation into the lack of reproducibility observed with earlier non-human primate SIV imaging and conflicting human studies.