99mTc-bioorthogonal click chemistry reagent for in vivo pretargeted imaging |
| |
| Institution: | 2. Petit Institute for Bioengineering and Bioscience, Atlanta, Georgia, USA;1. Czech Academy of Sciences, Institute of Biophysics, Kralovopolska 135, CZ-61265 Brno, Czech Republic;2. Department of Chemistry, Eastern Michigan University, Ypsilanti, MI 48197, USA;1. Vascular Biotechnology Laboratory, Baker IDI, Melbourne, Australia;2. Atherothrombosis and Vascular Biology Laboratory, Baker IDI, Melbourne, Australia;3. Departments of Nuclear Medicine and Centre for PET, Austin Hospital, Melbourne, Australia;4. Department of Medicine, Dentistry and Health Sciences, The University of Melbourne, Melbourne, Australia;5. Ludwig Institute for Cancer Research, Austin Hospital, Melbourne, Australia;6. The Florey Institute of Neuroscience and Mental Health, Austin Hospital, Melbourne, Australia;7. Central Clinical School, Monash University, Melbourne, Australia;1. Molecular Imaging Center Antwerp, University of Antwerp, Antwerp, Belgium;2. University Hospital Antwerp, Department of Nuclear Medicine, Edegem, Belgium;3. Laboratory of Medicinal Chemistry, University of Antwerp, Antwerp, Belgium;4. Department of Translational Neurosciences, University of Antwerp, Belgium |
| |
| 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 99mTc-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 99mTc at an efficiency of >95% and was radiochemically stable. 99mTc–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 99mTc–HYNIC–tetrazine for tumor imaging with pretargeted mAbs. |
| |
| Keywords: | Pretargeted imaging Click chemistry Monoclonal antibody |
| 本文献已被 ScienceDirect 等数据库收录！ |
|
