Development of18F-Labeled Bispyridyl Tetrazines for In Vivo Pretargeted PET Imaging

Research output: Contribution to journalJournal articlepeer-review

Standard

Development of18F-Labeled Bispyridyl Tetrazines for In Vivo Pretargeted PET Imaging. / García-Vázquez, Rocío; Jørgensen, Jesper Tranekjær; Bratteby, Klas Erik; Shalgunov, Vladimir; Hvass, Lars; Herth, Matthias M.; Kjær, Andreas; Battisti, Umberto Maria.

In: Pharmaceuticals, Vol. 15, No. 2, 245, 2022.

Research output: Contribution to journalJournal articlepeer-review

Harvard

García-Vázquez, R, Jørgensen, JT, Bratteby, KE, Shalgunov, V, Hvass, L, Herth, MM, Kjær, A & Battisti, UM 2022, 'Development of18F-Labeled Bispyridyl Tetrazines for In Vivo Pretargeted PET Imaging', Pharmaceuticals, vol. 15, no. 2, 245. https://doi.org/10.3390/ph15020245

APA

García-Vázquez, R., Jørgensen, J. T., Bratteby, K. E., Shalgunov, V., Hvass, L., Herth, M. M., Kjær, A., & Battisti, U. M. (2022). Development of18F-Labeled Bispyridyl Tetrazines for In Vivo Pretargeted PET Imaging. Pharmaceuticals, 15(2), [245]. https://doi.org/10.3390/ph15020245

Vancouver

García-Vázquez R, Jørgensen JT, Bratteby KE, Shalgunov V, Hvass L, Herth MM et al. Development of18F-Labeled Bispyridyl Tetrazines for In Vivo Pretargeted PET Imaging. Pharmaceuticals. 2022;15(2). 245. https://doi.org/10.3390/ph15020245

Author

García-Vázquez, Rocío ; Jørgensen, Jesper Tranekjær ; Bratteby, Klas Erik ; Shalgunov, Vladimir ; Hvass, Lars ; Herth, Matthias M. ; Kjær, Andreas ; Battisti, Umberto Maria. / Development of18F-Labeled Bispyridyl Tetrazines for In Vivo Pretargeted PET Imaging. In: Pharmaceuticals. 2022 ; Vol. 15, No. 2.

Bibtex

@article{b80216051dfa4533a68ba3944bcf8402,
title = "Development of18F-Labeled Bispyridyl Tetrazines for In Vivo Pretargeted PET Imaging",
abstract = "Pretargeted PET imaging is an emerging and fast-developing method to monitor immunooncology strategies. Currently, tetrazine ligation is considered the most promising bioorthogonal reaction for pretargeting in vivo. Recently, we have developed a method to18F-label ultrareactive tetrazines by copper-mediated fluorinations. However, bispyridyl tetrazines—one of the most promising structures for in vivo pretargeted applications—were inaccessible using this strategy. We believed that our successful efforts to18F-label H-tetrazines using low basic labeling conditions could also be used to label bispyridyl tetrazines via aliphatic nucleophilic substitution. Here, we report the first direct18F-labeling of bispyridyl tetrazines, their optimization for in vivo use, as well as their successful application in pretargeted PET imaging. This strategy resulted in the design of [18F]45, which could be labeled in a satisfactorily radiochemical yield (RCY = 16%), molar activity (Am = 57 GBq/µmol), and high radiochemical purity (RCP > 98%). The [18F]45 displayed a target-to-background ratio comparable to previously successfully applied tracers for pretargeted imaging. This study showed that bispyridyl tetrazines can be developed into pretargeted imaging agents. These structures allow an easy chemical modification of18F-labeled tetrazines, paving the road toward highly functionalized pretargeting tools. Moreover, bispyridyl tetrazines led to near-instant drug release of iTCO-tetrazine-based {\textquoteleft}click-to-release{\textquoteright} reactions. Consequently,18F-labeled bispyridyl tetrazines bear the possibility to quantify such release in vivo in the future.",
keywords = "Bioorthogonal chemistry, Bispyridyl tetrazines, Fluorine-18, Molecular imaging, PET, Pretargeted imaging, Tetrazine ligation",
author = "Roc{\'i}o Garc{\'i}a-V{\'a}zquez and J{\o}rgensen, {Jesper Tranekj{\ae}r} and Bratteby, {Klas Erik} and Vladimir Shalgunov and Lars Hvass and Herth, {Matthias M.} and Andreas Kj{\ae}r and Battisti, {Umberto Maria}",
note = "Funding Information: This project received funding from the European Union?s EU Framework Programme for Research and Innovation Horizon 2020 under grant agreement no. 668,532, and from the European Union?s Horizon 2020 research and innovation program under the Marie Sk?odowska-Curie grant agreement no. 813528. A.K. and M.M.H. received funding from the European Union?s EU Framework Programme for Research and Innovation Horizon 2020 (grant agreement no. 670261). V.S. was supported by the Lundbeck Foundation (R303-2018-3567) and by the BRIDGE Translational Excellence Programme at the Faculty of Health and Medical Sciences, University of Copenhagen, funded by the Novo Nordisk Foundation (grant agreement no. NNF18SA0034956). The Lundbeck Foundation, theNovo Nordisk Foundation, the Innovation Fund Denmark, and the Research Council for Independent Research (grant agreement no. 8022-00187B) are further acknowledged.The modified antibody used in this study was kindly provided by Tagworks Pharmaceuticals. Funding Information: Funding: This project received funding from the European Union{\textquoteright}s EU Framework Programme for Research and Innovation Horizon 2020 under grant agreement no. 668,532, and from the European Union{\textquoteright}s Horizon 2020 research and innovation program under the Marie Sk{\l}odowska-Curie grant agreement no. 813528. A.K. and M.M.H. received funding from the European Union{\textquoteright}s EU Framework Programme for Research and Innovation Horizon 2020 (grant agreement no. 670261). V.S. was supported by the Lundbeck Foundation (R303-2018-3567) and by the BRIDGE Translational Excellence Programme at the Faculty of Health and Medical Sciences, University of Copenhagen, funded by the Novo Nordisk Foundation (grant agreement no. NNF18SA0034956). The Lundbeck Foundation, the Novo Nordisk Foundation, the Innovation Fund Denmark, and the Research Council for Independent Research (grant agreement no. 8022-00187B) are further acknowledged. Publisher Copyright: {\textcopyright} 2022 by the authors. Licensee MDPI, Basel, Switzerland.",
year = "2022",
doi = "10.3390/ph15020245",
language = "English",
volume = "15",
journal = "Pharmaceuticals",
issn = "1424-8247",
publisher = "M D P I AG",
number = "2",

}

RIS

TY - JOUR

T1 - Development of18F-Labeled Bispyridyl Tetrazines for In Vivo Pretargeted PET Imaging

AU - García-Vázquez, Rocío

AU - Jørgensen, Jesper Tranekjær

AU - Bratteby, Klas Erik

AU - Shalgunov, Vladimir

AU - Hvass, Lars

AU - Herth, Matthias M.

AU - Kjær, Andreas

AU - Battisti, Umberto Maria

N1 - Funding Information: This project received funding from the European Union?s EU Framework Programme for Research and Innovation Horizon 2020 under grant agreement no. 668,532, and from the European Union?s Horizon 2020 research and innovation program under the Marie Sk?odowska-Curie grant agreement no. 813528. A.K. and M.M.H. received funding from the European Union?s EU Framework Programme for Research and Innovation Horizon 2020 (grant agreement no. 670261). V.S. was supported by the Lundbeck Foundation (R303-2018-3567) and by the BRIDGE Translational Excellence Programme at the Faculty of Health and Medical Sciences, University of Copenhagen, funded by the Novo Nordisk Foundation (grant agreement no. NNF18SA0034956). The Lundbeck Foundation, theNovo Nordisk Foundation, the Innovation Fund Denmark, and the Research Council for Independent Research (grant agreement no. 8022-00187B) are further acknowledged.The modified antibody used in this study was kindly provided by Tagworks Pharmaceuticals. Funding Information: Funding: This project received funding from the European Union’s EU Framework Programme for Research and Innovation Horizon 2020 under grant agreement no. 668,532, and from the European Union’s Horizon 2020 research and innovation program under the Marie Skłodowska-Curie grant agreement no. 813528. A.K. and M.M.H. received funding from the European Union’s EU Framework Programme for Research and Innovation Horizon 2020 (grant agreement no. 670261). V.S. was supported by the Lundbeck Foundation (R303-2018-3567) and by the BRIDGE Translational Excellence Programme at the Faculty of Health and Medical Sciences, University of Copenhagen, funded by the Novo Nordisk Foundation (grant agreement no. NNF18SA0034956). The Lundbeck Foundation, the Novo Nordisk Foundation, the Innovation Fund Denmark, and the Research Council for Independent Research (grant agreement no. 8022-00187B) are further acknowledged. Publisher Copyright: © 2022 by the authors. Licensee MDPI, Basel, Switzerland.

PY - 2022

Y1 - 2022

N2 - Pretargeted PET imaging is an emerging and fast-developing method to monitor immunooncology strategies. Currently, tetrazine ligation is considered the most promising bioorthogonal reaction for pretargeting in vivo. Recently, we have developed a method to18F-label ultrareactive tetrazines by copper-mediated fluorinations. However, bispyridyl tetrazines—one of the most promising structures for in vivo pretargeted applications—were inaccessible using this strategy. We believed that our successful efforts to18F-label H-tetrazines using low basic labeling conditions could also be used to label bispyridyl tetrazines via aliphatic nucleophilic substitution. Here, we report the first direct18F-labeling of bispyridyl tetrazines, their optimization for in vivo use, as well as their successful application in pretargeted PET imaging. This strategy resulted in the design of [18F]45, which could be labeled in a satisfactorily radiochemical yield (RCY = 16%), molar activity (Am = 57 GBq/µmol), and high radiochemical purity (RCP > 98%). The [18F]45 displayed a target-to-background ratio comparable to previously successfully applied tracers for pretargeted imaging. This study showed that bispyridyl tetrazines can be developed into pretargeted imaging agents. These structures allow an easy chemical modification of18F-labeled tetrazines, paving the road toward highly functionalized pretargeting tools. Moreover, bispyridyl tetrazines led to near-instant drug release of iTCO-tetrazine-based ‘click-to-release’ reactions. Consequently,18F-labeled bispyridyl tetrazines bear the possibility to quantify such release in vivo in the future.

AB - Pretargeted PET imaging is an emerging and fast-developing method to monitor immunooncology strategies. Currently, tetrazine ligation is considered the most promising bioorthogonal reaction for pretargeting in vivo. Recently, we have developed a method to18F-label ultrareactive tetrazines by copper-mediated fluorinations. However, bispyridyl tetrazines—one of the most promising structures for in vivo pretargeted applications—were inaccessible using this strategy. We believed that our successful efforts to18F-label H-tetrazines using low basic labeling conditions could also be used to label bispyridyl tetrazines via aliphatic nucleophilic substitution. Here, we report the first direct18F-labeling of bispyridyl tetrazines, their optimization for in vivo use, as well as their successful application in pretargeted PET imaging. This strategy resulted in the design of [18F]45, which could be labeled in a satisfactorily radiochemical yield (RCY = 16%), molar activity (Am = 57 GBq/µmol), and high radiochemical purity (RCP > 98%). The [18F]45 displayed a target-to-background ratio comparable to previously successfully applied tracers for pretargeted imaging. This study showed that bispyridyl tetrazines can be developed into pretargeted imaging agents. These structures allow an easy chemical modification of18F-labeled tetrazines, paving the road toward highly functionalized pretargeting tools. Moreover, bispyridyl tetrazines led to near-instant drug release of iTCO-tetrazine-based ‘click-to-release’ reactions. Consequently,18F-labeled bispyridyl tetrazines bear the possibility to quantify such release in vivo in the future.

KW - Bioorthogonal chemistry

KW - Bispyridyl tetrazines

KW - Fluorine-18

KW - Molecular imaging

KW - PET

KW - Pretargeted imaging

KW - Tetrazine ligation

U2 - 10.3390/ph15020245

DO - 10.3390/ph15020245

M3 - Journal article

C2 - 35215356

AN - SCOPUS:85125202857

VL - 15

JO - Pharmaceuticals

JF - Pharmaceuticals

SN - 1424-8247

IS - 2

M1 - 245

ER -

ID: 300065996