A new highly reactive and low lipophilicity fluorine-18 labeled tetrazine derivative for pretargeted PET imaging Journal Article
| Authors: | Keinänen, O.; Li, X. G.; Chenna, N. K.; Lumen, D.; Ott, J.; Molthoff, C. F. M.; Sarparanta, M.; Helariutta, K.; Vuorinen, T.; Windhorst, A. D.; Airaksinen, A. J. |
| Article Title: | A new highly reactive and low lipophilicity fluorine-18 labeled tetrazine derivative for pretargeted PET imaging |
| Abstract: | A new 18F-labeled tetrazine derivative was developed aiming at optimal radiochemistry, fast reaction kinetics in inverse electron-demand Diels-Alder cycloaddition (IEDDA), and favorable pharmacokinetics for in vivo bioorthogonal chemistry. The radiolabeling of the tetrazine was achieved in high yield, purity, and specific activity under mild reaction conditions via conjugation with 5-[18F]fluoro-5-deoxyribose, providing a glycosylated tetrazine derivative with low lipophilicity. The 18F-tetrazine showed fast reaction kinetics toward the most commonly used dienophiles in IEDDA reactions. It exhibited excellent chemical and enzymatic stability in mouse plasma and in phosphate-buffered saline (pH 7.41). Biodistribution in mice revealed favorable pharmacokinetics with major elimination via urinary excretion. The results indicate that the glycosylated 18F-labeled tetrazine is an excellent candidate for in vivo bioorthogonal chemistry applications in pretargeted PET imaging approaches. © 2015 American Chemical Society. |
| Keywords: | controlled study; unclassified drug; nonhuman; positron emission tomography; mouse; animal experiment; in vivo study; in vitro study; enzyme phosphorylation; kinetics; isotope labeling; radioactivity; pet imaging; high performance liquid chromatography; catalyst; diels alder reaction; lipophilicity; room temperature; extracellular space; circulation time; radiochemistry; drug elimination; click chemistry; isomerization; urinary excretion; chemical reaction kinetics; tetrazine derivative; male; priority journal; article; pet-ct scanner; tetrazine; bioorthogonal chemistry; tetrazine f 18 |
| Journal Title: | ACS Medicinal Chemistry Letters |
| Volume: | 7 |
| Issue: | 1 |
| ISSN: | 1948-5875 |
| Publisher: | American Chemical Society |
| Date Published: | 2016-01-14 |
| Start Page: | 62 |
| End Page: | 66 |
| Language: | English |
| DOI: | 10.1021/acsmedchemlett.5b00330 |
| PROVIDER: | scopus |
| PMCID: | PMC4716598 |
| PUBMED: | 26819667 |
| PMCID: | PMC4716598 |
| PUBMED: | 26819667 |
| DOI/URL: | |
| Notes: | Article -- Export Date: 3 March 2016 -- Source: Scopus |
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