PET imaging of HIV-1 envelope protein gp120 using 18F-labeled nanobodies
Neysha Martinez-Orengo,
Swati Shah,
Jianhao Lai,
Falguni Basuli,
Anna Lyndaker,
Mitchell L. Turner,
Morteza Peiravi,
Suman Sourabh,
Kevon Sampson,
Peng Zhang,
Rolf E. Swenson,
Paolo Lusso,
Frank Maldarelli,
Avindra Nath,
Chuen-Yen Lau,
Dima A. Hammoud
Affiliations
Neysha Martinez-Orengo
Center for Infectious Disease Imaging (CIDI), Radiology and Imaging Sciences, Clinical Center (CC), National Institutes of Health, Bethesda, MD, USA
Swati Shah
Center for Infectious Disease Imaging (CIDI), Radiology and Imaging Sciences, Clinical Center (CC), National Institutes of Health, Bethesda, MD, USA
Jianhao Lai
Center for Infectious Disease Imaging (CIDI), Radiology and Imaging Sciences, Clinical Center (CC), National Institutes of Health, Bethesda, MD, USA
Falguni Basuli
Chemistry and Synthesis Center, National Heart, Lung, and Blood Institute (NHLBI), National Institutes of Health, Rockville, MD, USA
Anna Lyndaker
Center for Infectious Disease Imaging (CIDI), Radiology and Imaging Sciences, Clinical Center (CC), National Institutes of Health, Bethesda, MD, USA
Mitchell L. Turner
Center for Infectious Disease Imaging (CIDI), Radiology and Imaging Sciences, Clinical Center (CC), National Institutes of Health, Bethesda, MD, USA
Morteza Peiravi
Center for Infectious Disease Imaging (CIDI), Radiology and Imaging Sciences, Clinical Center (CC), National Institutes of Health, Bethesda, MD, USA
Suman Sourabh
Center for Infectious Disease Imaging (CIDI), Radiology and Imaging Sciences, Clinical Center (CC), National Institutes of Health, Bethesda, MD, USA
Kevon Sampson
Division of Neuroimmunology and Neurovirology, National Institute of Neurological Disorders and Stroke (NINDS), National Institutes of Health, Bethesda, MD, USA
Peng Zhang
Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health, Bethesda, MD, USA
Rolf E. Swenson
Chemistry and Synthesis Center, National Heart, Lung, and Blood Institute (NHLBI), National Institutes of Health, Rockville, MD, USA
Paolo Lusso
Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health, Bethesda, MD, USA
Frank Maldarelli
HIV Dynamics and Replication Program, Center for Cancer Research, National Cancer Institute (NCI), National Institutes of Health, Bethesda, MD, USA
Avindra Nath
Division of Neuroimmunology and Neurovirology, National Institute of Neurological Disorders and Stroke (NINDS), National Institutes of Health, Bethesda, MD, USA
Chuen-Yen Lau
HIV Dynamics and Replication Program, Center for Cancer Research, National Cancer Institute (NCI), National Institutes of Health, Bethesda, MD, USA; Corresponding author
Dima A. Hammoud
Center for Infectious Disease Imaging (CIDI), Radiology and Imaging Sciences, Clinical Center (CC), National Institutes of Health, Bethesda, MD, USA; Corresponding author
Summary: Radiolabeled antibodies against the HIV-1 envelope protein, gp120, have been previously tested in animal models and in people with HIV (PWH). Nanobodies offer advantages over antibodies, including smaller size and faster clearance, which allow labeling with fluorine-18. In this study, three nanobodies (J3, 3E3, B9) chosen based on their binding properties to the conserved CD4-binding site of gp120 were labeled with fluorine-18 and used for PET imaging in mice bearing wild-type (WT) and/or gp120-expressing (Env+) tumors. [18F]J3 and [18F]3E3 selectively targeted Env+ tumors and not WT tumors, with minimal background signal. Switching from non-site-specific radiolabeling method to sortase A-mediated site-specific conjugation at the C-terminus improved binding to Env+ tumors for all nanobodies. Site-specifically 18F-labeled J3 nanobody is the most promising candidate with the highest level of binding. These results establish an Env+ imaging method that will enable next stage testing in an HIV-1 preclinical infection model and potentially in PWH.
