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Development of a 18 F‐Labeled Tetrazine with Favorable Pharmacokinetics for Bioorthogonal PET Imaging
Author(s) -
Denk Christoph,
Svatunek Dennis,
Filip Thomas,
Wanek Thomas,
Lumpi Daniel,
Fröhlich Johannes,
Kuntner Claudia,
Mikula Hannes
Publication year - 2014
Publication title -
angewandte chemie international edition
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.831
H-Index - 550
eISSN - 1521-3773
pISSN - 1433-7851
DOI - 10.1002/anie.201404277
Subject(s) - tetrazine , bioorthogonal chemistry , pharmacokinetics , radiochemistry , pet imaging , chemistry , nuclear medicine , positron emission tomography , combinatorial chemistry , medicine , pharmacology , organic chemistry , click chemistry
A low‐molecular‐weight 18 F‐labeled tetrazine derivative was developed as a highly versatile tool for bioorthogonal PET imaging. Prosthetic groups and undesired carrying of 18 F through additional steps were evaded by direct 18 F‐fluorination of an appropriate tetrazine precursor. Reaction kinetics of the cycloaddition with trans‐cyclooctenes were investigated by applying quantum chemical calculations and stopped‐flow measurements in human plasma; the results indicated that the labeled tetrazine is suitable as a bioorthogonal probe for the imaging of dienophile‐tagged (bio)molecules. In vitro and in vivo investigations revealed high stability and PET/MRI in mice showed fast homogeneous biodistribution of the 18 F‐labeled tetrazine that also passes the blood–brain barrier. An in vivo click experiment confirmed the bioorthogonal behavior of this novel tetrazine probe. Due to favorable chemical and pharmacokinetic properties this bioorthogonal agent should find application in bioimaging and biomedical research.