Development of the First Aliphatic 18F‑Labeled Tetrazine Suitable for Pretargeted PET ImagingExpanding the Bioorthogonal Tool Box
Pretargeted imaging of nanomedicines have attracted considerable interest because it has the potential to increase imaging contrast while reducing radiation burden to healthy tissue. Currently, the tetrazine ligation is the fastest bioorthogonal reaction for this strategy and, consequently, the stat...
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Published in | Journal of medicinal chemistry Vol. 64; no. 20; pp. 15297 - 15312 |
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Main Authors | , , , , , , , |
Format | Journal Article |
Language | English |
Published |
American Chemical Society
28.10.2021
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Online Access | Get full text |
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Abstract | Pretargeted imaging of nanomedicines have attracted considerable interest because it has the potential to increase imaging contrast while reducing radiation burden to healthy tissue. Currently, the tetrazine ligation is the fastest bioorthogonal reaction for this strategy and, consequently, the state-of-art choice for in vivo chemistry. We have recently identified key properties for tetrazines in pretargeting. We have also developed a method to 18F-label reactive tetrazines using an aliphatic nucleophilic substitution strategy. Here, we combined this knowledge and developed an 18F-labeled tetrazine for pretargeted imaging. In order to develop this ligand, a small SAR study was performed. The most promising compound was selected for labeling and subsequent positron-emission-tomography in vivo imaging. Radiolabeling was achieved in satisfactory yields, molar activities, and high radiochemical purities. [18F]15 displayed favorable pharmacokinetics and remarkable target-to-background ratiosas early as 1 h post injection. We believe that this agent could be a promising candidate for translation into clinical studies. |
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AbstractList | Pretargeted imaging of nanomedicines have attracted considerable interest because it has the potential to increase imaging contrast while reducing radiation burden to healthy tissue. Currently, the tetrazine ligation is the fastest bioorthogonal reaction for this strategy and, consequently, the state-of-art choice for in vivo chemistry. We have recently identified key properties for tetrazines in pretargeting. We have also developed a method to 18F-label reactive tetrazines using an aliphatic nucleophilic substitution strategy. Here, we combined this knowledge and developed an 18F-labeled tetrazine for pretargeted imaging. In order to develop this ligand, a small SAR study was performed. The most promising compound was selected for labeling and subsequent positron-emission-tomography in vivo imaging. Radiolabeling was achieved in satisfactory yields, molar activities, and high radiochemical purities. [18F]15 displayed favorable pharmacokinetics and remarkable target-to-background ratiosas early as 1 h post injection. We believe that this agent could be a promising candidate for translation into clinical studies. |
Author | Jørgensen, Jesper T Battisti, Umberto M Mikula, Hannes Shalgunov, Vladimir Hvass, Lars Kjær, Andreas Herth, Matthias Manfred Bratteby, Klas |
AuthorAffiliation | Department of Radiation Physics Rigshospitalet Skåne University Hospital Technische Universität Wien (TU Wien) Department of Drug Design and Pharmacology, Faculty of Health and Medical Sciences Cluster for Molecular Imaging, Department of Biomedical Sciences University of Copenhagen Institute of Applied Synthetic Chemistry Department of Clinical Physiology, Nuclear Medicine & PET |
AuthorAffiliation_xml | – name: Department of Radiation Physics – name: Skåne University Hospital – name: Institute of Applied Synthetic Chemistry – name: Cluster for Molecular Imaging, Department of Biomedical Sciences – name: Department of Drug Design and Pharmacology, Faculty of Health and Medical Sciences – name: Rigshospitalet – name: University of Copenhagen – name: Department of Clinical Physiology, Nuclear Medicine & PET – name: Technische Universität Wien (TU Wien) |
Author_xml | – sequence: 1 givenname: Umberto M surname: Battisti fullname: Battisti, Umberto M organization: Department of Drug Design and Pharmacology, Faculty of Health and Medical Sciences – sequence: 2 givenname: Klas orcidid: 0000-0003-0930-2390 surname: Bratteby fullname: Bratteby, Klas organization: Skåne University Hospital – sequence: 3 givenname: Jesper T surname: Jørgensen fullname: Jørgensen, Jesper T organization: University of Copenhagen – sequence: 4 givenname: Lars surname: Hvass fullname: Hvass, Lars organization: University of Copenhagen – sequence: 5 givenname: Vladimir surname: Shalgunov fullname: Shalgunov, Vladimir organization: Department of Drug Design and Pharmacology, Faculty of Health and Medical Sciences – sequence: 6 givenname: Hannes orcidid: 0000-0002-9218-9722 surname: Mikula fullname: Mikula, Hannes organization: Technische Universität Wien (TU Wien) – sequence: 7 givenname: Andreas orcidid: 0000-0002-2706-5547 surname: Kjær fullname: Kjær, Andreas organization: University of Copenhagen – sequence: 8 givenname: Matthias Manfred orcidid: 0000-0002-7788-513X surname: Herth fullname: Herth, Matthias Manfred email: matthias.herth@sund.ku.dk organization: Rigshospitalet |
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Title | Development of the First Aliphatic 18F‑Labeled Tetrazine Suitable for Pretargeted PET ImagingExpanding the Bioorthogonal Tool Box |
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