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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| Main Authors: | , , , |
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| Format: | Article |
| Language: | English |
| Published: |
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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| Summary: | 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. |
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| ISSN: | 2045-2322 |