PET imaging of AAV9 and AAVBR1 trafficking in normal mice
Abstract Adeno-associated virus (AAV) mediated gene therapy is advancing and needs a noninvasive imaging tool to evaluate its effective targeting, biodistribution and clearance for precise use in humans. In this study, two serotypes of AAVs, AAV9-CMV-fLuc, and a brain targeting variant, AAVBR1-CMV-f...
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Nature Portfolio
2025-02-01
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| Series: | Scientific Reports |
| Online Access: | https://doi.org/10.1038/s41598-025-86815-0 |
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| author | Aditya Bansal Shalini Sharma Manasa Kethamreddy Mukesh K. Pandey |
| author_facet | Aditya Bansal Shalini Sharma Manasa Kethamreddy Mukesh K. Pandey |
| author_sort | Aditya Bansal |
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| description | Abstract Adeno-associated virus (AAV) mediated gene therapy is advancing and needs a noninvasive imaging tool to evaluate its effective targeting, biodistribution and clearance for precise use in humans. In this study, two serotypes of AAVs, AAV9-CMV-fLuc, and a brain targeting variant, AAVBR1-CMV-fLuc, are directly radiolabeled with the positron emission tomography (PET) radioisotope, 89Zr. A radiolabeling synthon, [89Zr]Zr-DFO-Bn-NCS or [89Zr]Zr-DBN, was employed for the direct radiolabeling of AAVs, which enables tracking of AAVs by PET imaging for up to 18 days post-injection. The 89Zr radiolabeled AAVs were administered to BALB/c mice via tail vein and assessed for their biodistribution at various time points up to day 18 post-injection. Imaging of AAVs was followed by ex-vivo biodistribution at day 18, or luciferase imaging at 3rd week or > 30 days post-injection. The two serotypes showed differences in their biodistribution and trafficking in mice as early as 10 min post-injection. The brain targeting serotype, [89Zr]Zr-AAVBR1-CMV-fLuc, showed significantly higher uptake in the brain as compared to [89Zr]Zr-AAV9-CMV-fLuc. The luciferase expression-based infection profile correlated with both PET imaging and ex-vivo biodistribution data. The developed methodology provides a noninvasive approach to image the pharmacokinetics of AAVs in a longitudinal manner and renders a selection of specific AAV serotypes for tissue/organ specific targeting. |
| format | Article |
| id | doaj-art-6725eb33e9fc4d2a8704ddb0fcd9bffb |
| institution | Kabale University |
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| language | English |
| publishDate | 2025-02-01 |
| publisher | Nature Portfolio |
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| series | Scientific Reports |
| spelling | doaj-art-6725eb33e9fc4d2a8704ddb0fcd9bffb2025-02-09T12:33:16ZengNature PortfolioScientific Reports2045-23222025-02-0115111610.1038/s41598-025-86815-0PET imaging of AAV9 and AAVBR1 trafficking in normal miceAditya Bansal0Shalini Sharma1Manasa Kethamreddy2Mukesh K. Pandey3Division of Nuclear Medicine, Department of Radiology, Mayo ClinicDivision of Nuclear Medicine, Department of Radiology, Mayo ClinicDivision of Nuclear Medicine, Department of Radiology, Mayo ClinicDivision of Nuclear Medicine, Department of Radiology, Mayo ClinicAbstract Adeno-associated virus (AAV) mediated gene therapy is advancing and needs a noninvasive imaging tool to evaluate its effective targeting, biodistribution and clearance for precise use in humans. In this study, two serotypes of AAVs, AAV9-CMV-fLuc, and a brain targeting variant, AAVBR1-CMV-fLuc, are directly radiolabeled with the positron emission tomography (PET) radioisotope, 89Zr. A radiolabeling synthon, [89Zr]Zr-DFO-Bn-NCS or [89Zr]Zr-DBN, was employed for the direct radiolabeling of AAVs, which enables tracking of AAVs by PET imaging for up to 18 days post-injection. The 89Zr radiolabeled AAVs were administered to BALB/c mice via tail vein and assessed for their biodistribution at various time points up to day 18 post-injection. Imaging of AAVs was followed by ex-vivo biodistribution at day 18, or luciferase imaging at 3rd week or > 30 days post-injection. The two serotypes showed differences in their biodistribution and trafficking in mice as early as 10 min post-injection. The brain targeting serotype, [89Zr]Zr-AAVBR1-CMV-fLuc, showed significantly higher uptake in the brain as compared to [89Zr]Zr-AAV9-CMV-fLuc. The luciferase expression-based infection profile correlated with both PET imaging and ex-vivo biodistribution data. The developed methodology provides a noninvasive approach to image the pharmacokinetics of AAVs in a longitudinal manner and renders a selection of specific AAV serotypes for tissue/organ specific targeting.https://doi.org/10.1038/s41598-025-86815-0 |
| spellingShingle | Aditya Bansal Shalini Sharma Manasa Kethamreddy Mukesh K. Pandey PET imaging of AAV9 and AAVBR1 trafficking in normal mice Scientific Reports |
| title | PET imaging of AAV9 and AAVBR1 trafficking in normal mice |
| title_full | PET imaging of AAV9 and AAVBR1 trafficking in normal mice |
| title_fullStr | PET imaging of AAV9 and AAVBR1 trafficking in normal mice |
| title_full_unstemmed | PET imaging of AAV9 and AAVBR1 trafficking in normal mice |
| title_short | PET imaging of AAV9 and AAVBR1 trafficking in normal mice |
| title_sort | pet imaging of aav9 and aavbr1 trafficking in normal mice |
| url | https://doi.org/10.1038/s41598-025-86815-0 |
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