María Fernanda García1, Xiuli Zhang2, Manankumar Shah3, Jessica Newton-Northup4, Pablo Cabral5, Hugo Cerecetto6, Thomas Quinn7. 1. Área de Radiofarmacia, Centro de Investigaciones Nucleares, Facultad de Ciencias, Universidad de la República, Mataojo 2055, 11400 Montevideo, Uruguay. Electronic address: fgmelian@gmail.com. 2. 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. 3. 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. 4. 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. 5. Área de Radiofarmacia, Centro de Investigaciones Nucleares, Facultad de Ciencias, Universidad de la República, Mataojo 2055, 11400 Montevideo, Uruguay. Electronic address: pabloc7@gmail.com. 6. Área de Radiofarmacia, Centro de Investigaciones Nucleares, Facultad de Ciencias, Universidad de la República, Mataojo 2055, 11400 Montevideo, Uruguay. Electronic address: hcerecetto@gmail.com. 7. 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.
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.
Metal-free click chemistry has become an important tool for pretargeted approaches in the molecular imaging field. The application of bioorthogonal click chemistry ben class="Chemical">tween 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.
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