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

Following 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 used 89Zr-7D3 and 89Zr- 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-vivo probe uptake between SIVmac-infected and uninfected macaques, or ex-vivo validation necropsies. While the probes remained stable in-vivo, only 89Zr-ITS103.01LS-F(ab)2 in chronic plasma retained its binding specificity to SIV gp120, with 89Zr-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 HIV in-vivo, warranting further investigation into the lack of reproducibility observed with earlier non-human primate SIV imaging and conflicting human studies.