PET imaging of HIV-1 envelope protein gp120 using 18F-labeled nanobodies
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...
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Elsevier
2025-02-01
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2589004225000549 |
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| author | 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 |
| author_facet | 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 |
| author_sort | Neysha Martinez-Orengo |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-8dfcd83fa8074d8088a4e664cc5de8f7 |
| institution | Kabale University |
| issn | 2589-0042 |
| language | English |
| publishDate | 2025-02-01 |
| publisher | Elsevier |
| record_format | Article |
| series | iScience |
| spelling | doaj-art-8dfcd83fa8074d8088a4e664cc5de8f72025-01-28T04:14:49ZengElsevieriScience2589-00422025-02-01282111795PET imaging of HIV-1 envelope protein gp120 using 18F-labeled nanobodiesNeysha Martinez-Orengo0Swati Shah1Jianhao Lai2Falguni Basuli3Anna Lyndaker4Mitchell L. Turner5Morteza Peiravi6Suman Sourabh7Kevon Sampson8Peng Zhang9Rolf E. Swenson10Paolo Lusso11Frank Maldarelli12Avindra Nath13Chuen-Yen Lau14Dima A. Hammoud15Center for Infectious Disease Imaging (CIDI), Radiology and Imaging Sciences, Clinical Center (CC), National Institutes of Health, Bethesda, MD, USACenter for Infectious Disease Imaging (CIDI), Radiology and Imaging Sciences, Clinical Center (CC), National Institutes of Health, Bethesda, MD, USACenter for Infectious Disease Imaging (CIDI), Radiology and Imaging Sciences, Clinical Center (CC), National Institutes of Health, Bethesda, MD, USAChemistry and Synthesis Center, National Heart, Lung, and Blood Institute (NHLBI), National Institutes of Health, Rockville, MD, USACenter for Infectious Disease Imaging (CIDI), Radiology and Imaging Sciences, Clinical Center (CC), National Institutes of Health, Bethesda, MD, USACenter for Infectious Disease Imaging (CIDI), Radiology and Imaging Sciences, Clinical Center (CC), National Institutes of Health, Bethesda, MD, USACenter for Infectious Disease Imaging (CIDI), Radiology and Imaging Sciences, Clinical Center (CC), National Institutes of Health, Bethesda, MD, USACenter for Infectious Disease Imaging (CIDI), Radiology and Imaging Sciences, Clinical Center (CC), National Institutes of Health, Bethesda, MD, USADivision of Neuroimmunology and Neurovirology, National Institute of Neurological Disorders and Stroke (NINDS), National Institutes of Health, Bethesda, MD, USALaboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health, Bethesda, MD, USAChemistry and Synthesis Center, National Heart, Lung, and Blood Institute (NHLBI), National Institutes of Health, Rockville, MD, USALaboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health, Bethesda, MD, USAHIV Dynamics and Replication Program, Center for Cancer Research, National Cancer Institute (NCI), National Institutes of Health, Bethesda, MD, USADivision of Neuroimmunology and Neurovirology, National Institute of Neurological Disorders and Stroke (NINDS), National Institutes of Health, Bethesda, MD, USAHIV Dynamics and Replication Program, Center for Cancer Research, National Cancer Institute (NCI), National Institutes of Health, Bethesda, MD, USA; Corresponding authorCenter for Infectious Disease Imaging (CIDI), Radiology and Imaging Sciences, Clinical Center (CC), National Institutes of Health, Bethesda, MD, USA; Corresponding authorSummary: 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.http://www.sciencedirect.com/science/article/pii/S2589004225000549ImmunologyRadiology |
| spellingShingle | 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 PET imaging of HIV-1 envelope protein gp120 using 18F-labeled nanobodies iScience Immunology Radiology |
| title | PET imaging of HIV-1 envelope protein gp120 using 18F-labeled nanobodies |
| title_full | PET imaging of HIV-1 envelope protein gp120 using 18F-labeled nanobodies |
| title_fullStr | PET imaging of HIV-1 envelope protein gp120 using 18F-labeled nanobodies |
| title_full_unstemmed | PET imaging of HIV-1 envelope protein gp120 using 18F-labeled nanobodies |
| title_short | PET imaging of HIV-1 envelope protein gp120 using 18F-labeled nanobodies |
| title_sort | pet imaging of hiv 1 envelope protein gp120 using 18f labeled nanobodies |
| topic | Immunology Radiology |
| url | http://www.sciencedirect.com/science/article/pii/S2589004225000549 |
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