title: A New Highly Reactive and Low Lipophilicity Fluorine-18 Labeled Tetrazine Derivative for Pretargeted PET Imaging.
abstract: A new (18)F-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-[(18)F]fluoro-5-deoxyribose, providing a glycosylated tetrazine derivative with low lipophilicity. The (18)F-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 (18)F-labeled tetrazine is an excellent candidate for in vivo bioorthogonal chemistry applications in pretargeted PET imaging approaches.
authors.affiliation: Laboratory of Radiochemistry, Department of Chemistry, University of Helsinki , FI-00014 Helsinki, Finland.
authors.forename: Outi
authors.initials: O
authors.lastname: Keinänen
authors.affiliation: Turku Positron Emission Tomography (PET) Centre, University of Turku and Turku University Hospital , FI-20521 Turku, Finland.
authors.forename: Xiang-Guo
authors.initials: XG
authors.lastname: Li
authors.affiliation: Department of Forest Products Technology, Aalto University School of Chemical Technology , FI-00076 Espoo, Finland.
authors.forename: Naveen K
authors.initials: NK
authors.lastname: Chenna
authors.affiliation: Laboratory of Radiochemistry, Department of Chemistry, University of Helsinki , FI-00014 Helsinki, Finland.
authors.forename: Dave
authors.initials: D
authors.lastname: Lumen
authors.affiliation: Laboratory of Radiochemistry, Department of Chemistry, University of Helsinki , FI-00014 Helsinki, Finland.
authors.forename: Jennifer
authors.initials: J
authors.lastname: Ott
authors.affiliation: Department of Radiology and Nuclear Medicine, VU University Medical Center , 1081 HV Amsterdam, The Netherlands.
authors.forename: Carla F M
authors.initials: CF
authors.lastname: Molthoff
authors.affiliation: Laboratory of Radiochemistry, Department of Chemistry, University of Helsinki, FI-00014 Helsinki, Finland; Department of Radiology, Memorial Sloan Kettering Cancer Center, New York, New York 10065, United States.
authors.forename: Mirkka
authors.initials: M
authors.lastname: Sarparanta
authors.affiliation: Laboratory of Radiochemistry, Department of Chemistry, University of Helsinki , FI-00014 Helsinki, Finland.
authors.forename: Kerttuli
authors.initials: K
authors.lastname: Helariutta
authors.affiliation: Department of Forest Products Technology, Aalto University School of Chemical Technology , FI-00076 Espoo, Finland.
authors.forename: Tapani
authors.initials: T
authors.lastname: Vuorinen
authors.affiliation: Department of Radiology and Nuclear Medicine, VU University Medical Center , 1081 HV Amsterdam, The Netherlands.
authors.forename: Albert D
authors.initials: AD
authors.lastname: Windhorst
authors.affiliation: Laboratory of Radiochemistry, Department of Chemistry, University of Helsinki , FI-00014 Helsinki, Finland.
authors.forename: Anu J
authors.initials: AJ
authors.lastname: Airaksinen
keywords: Bioorthogonal chemistry; PET imaging; click chemistry; kinetics; tetrazine
references.citation: Nucl Med Biol. 1999 May;26(4):389-96
references.pmid: 10382842
references.citation: J Nucl Med. 2003 Aug;44(8):1284-92
references.pmid: 12902420
references.citation: Eur J Clin Pharmacol. 2003 Sep;59(5-6):357-66
references.pmid: 12937873
references.citation: Bioconjug Chem. 2005 Jan-Feb;16(1):43-50
references.pmid: 15656574
references.citation: Clin Pharmacol Ther. 2008 Feb;83(2):349-53
references.pmid: 18167503
references.citation: J Am Chem Soc. 2008 Oct 15;130(41):13518-9
references.pmid: 18798613
references.citation: Bioconjug Chem. 2008 Dec;19(12):2297-9
references.pmid: 19053305
references.citation: Eur J Nucl Med Mol Imaging. 2009 Sep;36(9):1469-74
references.pmid: 19350236
references.citation: Angew Chem Int Ed Engl. 2009;48(38):7013-6
references.pmid: 19697389
references.citation: Angew Chem Int Ed Engl. 2009;48(38):6974-98
references.pmid: 19714693
references.citation: Angew Chem Int Ed Engl. 2010 Apr 6;49(16):2869-72
references.pmid: 20306505
references.citation: Angew Chem Int Ed Engl. 2010 Apr 26;49(19):3375-8
references.pmid: 20391522
references.citation: Drug Discov Today. 2010 Aug;15(15-16):648-55
references.pmid: 20570751
references.citation: Chem Commun (Camb). 2010 Nov 14;46(42):8043-5
references.pmid: 20862423
references.citation: ChemMedChem. 2011 Mar 7;6(3):424-7
references.pmid: 21360818
references.citation: Acc Chem Res. 2011 Sep 20;44(9):666-76
references.pmid: 21838330
references.citation: Br J Clin Pharmacol. 2012 Feb;73(2):175-86
references.pmid: 21838787
references.citation: Chem Commun (Camb). 2012 May 28;48(43):5247-9
references.pmid: 22476360
references.citation: Expert Opin Drug Discov. 2012 Oct;7(10):863-75
references.pmid: 22992175
references.citation: Expert Opin Drug Discov. 2007 Jan;2(1):51-64
references.pmid: 23496037
references.citation: Chem Commun (Camb). 2013 May 8;49(36):3805-7
references.pmid: 23535705
references.citation: Chem Commun (Camb). 2013 May 7;49(35):3682-3684
references.pmid: 23536117
references.citation: Org Biomol Chem. 2013 Jun 21;11(23):3817-25
references.pmid: 23640655
references.citation: J Nucl Med. 2013 Aug;54(8):1389-96
references.pmid: 23708196
references.citation: Bioconjug Chem. 2013 Jul 17;24(7):1210-7
references.pmid: 23725393
references.citation: Org Biomol Chem. 2013 Sep 21;11(35):5772-81
references.pmid: 23907155
references.citation: Curr Opin Chem Biol. 2013 Oct;17(5):761-7
references.pmid: 24021760
references.citation: Am J Nucl Med Mol Imaging. 2014 Mar 20;4(2):96-113
references.pmid: 24753979
references.citation: Angew Chem Int Ed Engl. 2014 Sep 1;53(36):9655-9
references.pmid: 24989029
references.citation: Bioorg Med Chem Lett. 2014 Aug 15;24(16):3891-7
references.pmid: 25017032
references.citation: Bioconjug Chem. 2015 Jan 21;26(1):1-18
references.pmid: 25473848
references.citation: J Med Chem. 2015 Jul 23;58(14):5538-47
references.pmid: 26102222
references.citation: Chem Commun (Camb). 2015 Aug 11;51(62):12415-8
references.pmid: 26145162
references.citation: ACS Cent Sci. 2015 Jun 24;1(3):142-147
references.pmid: 26955657