Tetrazine-based cycloadditions: application to pretargeted live cell imaging.
Bioorthogonal tetrazine cycloadditions have been applied to live cell labeling. Tetrazines react irreversibly with the strained dienophile norbornene forming dihydropyrazine products and dinitrogen. The reaction is high yielding, selective, and fast in aqueous media. Her2/neu receptors on live human breast cancer cells were targeted with a monoclonal antibody modified with a norbornene. Tetrazines conjugated to a near-infrared fluorochrome selectively and rapidly label the pretargeted antibody in the presence of serum. These findings indicate that this chemistry is suitable for in vitro labeling experiments, and suggests that it may prove a useful strategy for in vivo pretargeted imaging under numerous modalities.
Devaraj
Neal K
NK
Center for Systems Biology, Massachusetts General Hospital/Harvard Medical School Boston, Massachusetts 02114, USA.
Weissleder
Ralph
R
Hilderbrand
Scott A
SA
D000475:Alkenes / Q000737:chemistry; D045744:Cell Line, Tumor; D002470:Cell Survival; D006573:Heterocyclic Compounds, 1-Ring / Q000737:chemistry* / Q000378:metabolism*; D006801:Humans; D008856:Microscopy, Fluorescence; D011719:Pyrazines / Q000737:chemistry* / Q000378:metabolism*; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism; D013194:Staining and Labeling; D013379:Substrate Specificity; D013997:Time Factors
D000475:Alkenes; D006573:Heterocyclic Compounds, 1-Ring; D011719:Pyrazines; D018719:Erb-b2 Receptor Tyrosine Kinases; C534588:3-(4-benzylamino)-1,2,4,5-tetrazine