A1 Refereed original research article in a scientific journal
A new highly reactive and low lipophilicity fluorine-18 labeled tetrazine derivative for pretargeted PET imaging
Authors: Outi Keinänen, Xiang-Guo Li, Naveen K Chenna, Dave Lumen, Jennifer Ott, Carla FM Molthoff, Mirkka Sarparanta, Kerttuli Helariutta, Tapani Vuorinen, Albert D Windhorst, Anu J Airaksinen
Publisher: American Chemical Society
Publication year: 2016
Journal: ACS Medicinal Chemistry Letters
Volume: 7
Issue: 1
First page : 62
Last page: 66
Number of pages: 5
ISSN: 1948-5875
DOI: https://doi.org/10.1021/acsmedchemlett.5b00330
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.
