Development of a 18F-Labeled Tetrazine with Favorable Pharmacokinetics for Bioorthogonal PET Imaging

被引：107

作者：

Denk, Christoph ^{[1
]}

Svatunek, Dennis ^{[1
]}

Filip, Thomas ^{[2
]}

Wanek, Thomas ^{[2
]}

Lumpi, Daniel ^{[1
]}

Froehlich, Johannes ^{[1
]}

Kuntner, Claudia ^{[2
]}

Mikula, Hannes ^{[1
]}

机构：

[1] Vienna Univ Technol, Inst Angew Synth Chem, Vienna, Austria

[2] Austrian Inst Technol, Hlth & Environm Dept, Seibersdorf, Austria

来源：

ANGEWANDTE CHEMIE-INTERNATIONAL EDITION | 2014年 / 53卷 / 36期

关键词：

bioorthogonal chemistry; click chemistry; imaging agents; kinetics; tetrazines; FREE CLICK CHEMISTRY; POSITRON-EMISSION-TOMOGRAPHY; IN-VIVO CHEMISTRY; TRANS-CYCLOOCTENE; LIGATION; STRATEGY; BINDING; KINASE; TAGS;

D O I：

10.1002/anie.201404277

中图分类号：

O6 [化学];

学科分类号：

0703 ;

摘要：

A low-molecular-weight F-18-labeled tetrazine derivative was developed as a highly versatile tool for bioorthogonal PET imaging. Prosthetic groups and undesired carrying of F-18 through additional steps were evaded by direct F-18-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 F-18-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.

引用

页码：9655 / 9659

页数：5

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