title: (125)I-Tetrazines and Inverse-Electron-Demand Diels-Alder Chemistry: A Convenient Radioiodination Strategy for Biomolecule Labeling, Screening, and Biodistribution Studies.
abstract: A convenient method to prepare radioiodinated tetrazines was developed, such that a bioorthogonal inverse electron demand Diels-Alder reaction can be used to label biomolecules with iodine-125 for in vitro screening and in vivo biodistribution studies. The tetrazine was prepared by employing a high-yielding oxidative halo destannylation reaction that concomitantly oxidized the dihydrotetrazine precursor. The product reacts quickly and efficiently with trans-cyclooctene derivatives. Utility was demonstrated through antibody and hormone labeling experiments and by evaluating products using standard analytical methods, in vitro assays, and quantitative biodistribution studies where the latter was performed in direct comparison to Bolton-Hunter and direct iodination methods. The approach described provides a convenient and advantageous alternative to conventional protein iodination methods that can expedite preclinical development and evaluation of biotherapeutics.
authors.affiliation: Department of Chemistry and Chemical Biology and ‡Centre for Probe Development and Commercialization, McMaster University , 1280 Main Street West, Hamilton, Ontario, Canada L8S 4M1.
authors.forename: Silvia A
authors.initials: SA
authors.lastname: Albu
authors.affiliation: Department of Chemistry and Chemical Biology and ‡Centre for Probe Development and Commercialization, McMaster University , 1280 Main Street West, Hamilton, Ontario, Canada L8S 4M1.
authors.forename: Salma A
authors.initials: SA
authors.lastname: Al-Karmi
authors.affiliation: Department of Chemistry and Chemical Biology and ‡Centre for Probe Development and Commercialization, McMaster University , 1280 Main Street West, Hamilton, Ontario, Canada L8S 4M1.
authors.forename: Alyssa
authors.initials: A
authors.lastname: Vito
authors.affiliation: Department of Chemistry and Chemical Biology and ‡Centre for Probe Development and Commercialization, McMaster University , 1280 Main Street West, Hamilton, Ontario, Canada L8S 4M1.
authors.forename: James P K
authors.initials: JP
authors.lastname: Dzandzi
authors.affiliation: Department of Chemistry and Chemical Biology and ‡Centre for Probe Development and Commercialization, McMaster University , 1280 Main Street West, Hamilton, Ontario, Canada L8S 4M1.
authors.forename: Aimen
authors.initials: A
authors.lastname: Zlitni
authors.affiliation: Department of Chemistry and Chemical Biology and ‡Centre for Probe Development and Commercialization, McMaster University , 1280 Main Street West, Hamilton, Ontario, Canada L8S 4M1.
authors.forename: Denis
authors.initials: D
authors.lastname: Beckford-Vera
authors.affiliation: Department of Chemistry and Chemical Biology and ‡Centre for Probe Development and Commercialization, McMaster University , 1280 Main Street West, Hamilton, Ontario, Canada L8S 4M1.
authors.forename: Megan
authors.initials: M
authors.lastname: Blacker
authors.affiliation: Department of Chemistry and Chemical Biology and ‡Centre for Probe Development and Commercialization, McMaster University , 1280 Main Street West, Hamilton, Ontario, Canada L8S 4M1.
authors.forename: Nancy
authors.initials: N
authors.lastname: Janzen
authors.affiliation: Department of Chemistry and Chemical Biology and ‡Centre for Probe Development and Commercialization, McMaster University , 1280 Main Street West, Hamilton, Ontario, Canada L8S 4M1.
authors.forename: Ramesh M
authors.initials: RM
authors.lastname: Patel
authors.affiliation: Department of Chemistry and Chemical Biology and ‡Centre for Probe Development and Commercialization, McMaster University , 1280 Main Street West, Hamilton, Ontario, Canada L8S 4M1.
authors.forename: Alfredo
authors.initials: A
authors.lastname: Capretta
authors.affiliation: Department of Chemistry and Chemical Biology and ‡Centre for Probe Development and Commercialization, McMaster University , 1280 Main Street West, Hamilton, Ontario, Canada L8S 4M1.
authors.forename: John F
authors.initials: JF
authors.lastname: Valliant
mesh_terms: D000818:Animals; D000906:Antibodies / Q000737:chemistry; D045744:Cell Line, Tumor; D018360:Crystallography, X-Ray; D061565:Cycloaddition Reaction; D034242:Cyclooctanes / Q000737:chemistry; D005260:Female; D006571:Heterocyclic Compounds / Q000737:chemistry; D006801:Humans; D007457:Iodine Radioisotopes / Q000737:chemistry* / Q000493:pharmacokinetics; D007553:Isotope Labeling / Q000379:methods*; D008810:Mice, Inbred C57BL; D011972:Receptor, Insulin / Q000378:metabolism; D014018:Tissue Distribution; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000276:immunology
chemical_list: D000906:Antibodies; D034242:Cyclooctanes; D006571:Heterocyclic Compounds; D007457:Iodine Radioisotopes; C000588866:KDR protein, human; D011972:Receptor, Insulin; D040301:Vascular Endothelial Growth Factor Receptor-2