title: (99m)Tc-bioorthogonal click chemistry reagent for in vivo pretargeted imaging.
abstract: Metal-free click chemistry has become an important tool for pretargeted approaches in the molecular imaging field. The application of bioorthogonal click chemistry between a pretargeted trans-cyclooctene (TCO) derivatized monoclonal antibody (mAb) and a (99m)Tc-modified 1,2,4,5-tetrazine for tumor imaging was examined in vitro and in vivo. The HYNIC tetrazine compound was synthesized and structurally characterized, confirming its identity. Radiolabeling studies demonstrated that the HYNIC tetrazine was labeled with (99m)Tc at an efficiency of >95% and was radiochemically stable. (99m)Tc-HYNIC tetrazine reacted with the TCO-CC49 mAb in vitro demonstrating its selective reactivity. In vivo biodistribution studies revealed non-specific liver and GI uptake due to the hydrophobic property of the compound, however pretargeted SPECT imaging studies demonstrated tumor visualization confirming the success of the cycloaddition reaction in vivo. These results demonstrated the potential of (99m)Tc-HYNIC-tetrazine for tumor imaging with pretargeted mAbs.
authors.affiliation: Área de Radiofarmacia, Centro de Investigaciones Nucleares, Facultad de Ciencias, Universidad de la República, Mataojo 2055, 11400 Montevideo, Uruguay. Electronic address: fgmelian@gmail.com.
authors.forename: María Fernanda
authors.initials: MF
authors.lastname: García
authors.affiliation: Department of Biochemistry, University of Missouri, Columbia, MO 65211, USA; Harry S. Truman Veterans' Administration Hospital, Columbia, MO 65201, USA. Electronic address: zhangxiu@missouri.edu.
authors.forename: Xiuli
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Department of Biochemistry, University of Missouri, Columbia, MO 65211, USA; Harry S. Truman Veterans' Administration Hospital, Columbia, MO 65201, USA. Electronic address: masvh4@mail.missouri.edu.
authors.forename: Manankumar
authors.initials: M
authors.lastname: Shah
authors.affiliation: Department of Biochemistry, University of Missouri, Columbia, MO 65211, USA; Harry S. Truman Veterans' Administration Hospital, Columbia, MO 65201, USA. Electronic address: newtonj@missouri.edu.
authors.forename: Jessica
authors.initials: J
authors.lastname: Newton-Northup
authors.affiliation: Área de Radiofarmacia, Centro de Investigaciones Nucleares, Facultad de Ciencias, Universidad de la República, Mataojo 2055, 11400 Montevideo, Uruguay. Electronic address: pabloc7@gmail.com.
authors.forename: Pablo
authors.initials: P
authors.lastname: Cabral
authors.affiliation: Área de Radiofarmacia, Centro de Investigaciones Nucleares, Facultad de Ciencias, Universidad de la República, Mataojo 2055, 11400 Montevideo, Uruguay. Electronic address: hcerecetto@gmail.com.
authors.forename: Hugo
authors.initials: H
authors.lastname: Cerecetto
authors.affiliation: Department of Biochemistry, University of Missouri, Columbia, MO 65211, USA; Harry S. Truman Veterans' Administration Hospital, Columbia, MO 65201, USA. Electronic address: quinnt@missouri.edu.
authors.forename: Thomas
authors.initials: T
authors.lastname: Quinn
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000737:chemistry; D045744:Cell Line, Tumor; D057930:Click Chemistry; D034242:Cyclooctanes / Q000737:chemistry; D006801:Humans; D051379:Mice; D057054:Molecular Imaging / Q000379:methods*; D015335:Molecular Probes / Q000737:chemistry* / Q000493:pharmacokinetics; D009374:Neoplasms, Experimental / Q000175:diagnosis / Q000378:metabolism; D015609:Organotechnetium Compounds / Q000737:chemistry* / Q000493:pharmacokinetics; D013777:Tetrazoles / Q000737:chemistry* / Q000493:pharmacokinetics; D014018:Tissue Distribution
chemical_list: D000911:Antibodies, Monoclonal; D034242:Cyclooctanes; D015335:Molecular Probes; D015609:Organotechnetium Compounds; D013777:Tetrazoles
keywords: (99m)Tc–HYNIC; Click chemistry; Monoclonal antibody; Pretargeted imaging