A1 Journal article – refereed
A new highly reactive and low lipophilicity fluorine-18 labeled tetrazine derivative for pretargeted PET imaging

List of 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 number: 7
Issue number: 1
Number of pages: 5


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.

Last updated on 2019-21-08 at 22:46