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[18F]J3 nanobody is a preclinical fluorine-18 labeled PET radiotracer developed for the non-invasive molecular imaging of HIV-1-infected cells and viral reservoirs. The active targeting moiety is the J3 nanobody, a camelid single-domain antibody fragment (VHH) that binds with high affinity (KD ~1.1 nM) to the conserved CD4-binding site of the HIV-1 envelope glycoprotein gp120, neutralizing a broad range of HIV-1 strains. The tracer can be prepared via non-site-specific labeling using the prosthetic group 6-[18F]FPy-TFP or via site-specific sortase A-mediated conjugation ([18F]sortag-J3). In preclinical models, the radiotracer demonstrates selective binding to gp120-expressing tumors with rapid clearance from background tissues, making it a promising candidate for identifying viral reservoirs in vivo.
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