Journal of Radiopharmaceuticals and Molecular Probes (대한방사성의약품학회지)

Korean Society of Radiopharmaceuticals and Molecular Probes (대한방사성의약품학회)
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Selective tyrosine conjugation with a newly synthesized PCB -TE2A-luminol bifunctional chelator

  • Subramani Rajkumar (Department of Molecular Medicine, Brain Korea 21 four KNU Convergence Educational Program of Biomedical Sciences for Creative Future Talents, School of Medicine, Kyungpook National University) ;
  • Hyun Park (Division of Applied RI, Korea Institute of Radiological and Medical Sciences) ;
  • Abhinav Bhise (Department of Molecular Medicine, Brain Korea 21 four KNU Convergence Educational Program of Biomedical Sciences for Creative Future Talents, School of Medicine, Kyungpook National University) ;
  • Seong Hwan Cho (Department of Molecular Medicine, Brain Korea 21 four KNU Convergence Educational Program of Biomedical Sciences for Creative Future Talents, School of Medicine, Kyungpook National University) ;
  • Jung Young Kim (Division of Applied RI, Korea Institute of Radiological and Medical Sciences) ;
  • Kyo Chul Lee (Division of Applied RI, Korea Institute of Radiological and Medical Sciences) ;
  • Jeongsoo Yoo (Department of Molecular Medicine, Brain Korea 21 four KNU Convergence Educational Program of Biomedical Sciences for Creative Future Talents, School of Medicine, Kyungpook National University)
  • Received : 2021.11.22
  • Accepted : 2021.12.28
  • Published : 2021.12.30
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Abstract

Selective amino acid conjugation of bulky antibodies is a valuable asset for real-time diagnosis and therapy. However, selective conjugation incorporating a chelate-bearing radioactive atom into an antibody without affecting its immunoreactivity is a challenging task. A bifunctional chelator (BFC), a selective amino acid-targeting probe, and a linker have been developed to overcome this problem. Here, we report the synthesis of a novel propylene cross-bridged chelator (PCB)-1,8-N,N'-bis-(carboxymethyl)-1,4,8,11-tetraazacyclotetradecane (TE2A)-luminol BFC via a click reaction and radiolabel it with a 64Cu ion for tyrosine-selective conjugation of trastuzumab. In the initial optimization study, we tried different oxidative addition conditions such as electro-oxidation, hemin, horseradish peroxidase, iodogen tube, chloramine-T, and iodo beads. In this study, up to 82% of 64Cu-PCB-TE2A-luminol was conjugated with the antibody in an iodo bead-catalyzed oxidative addition reaction with an isolated yield of 24.4%.

Keywords

Acknowledgement

This work was supported by an R&D program through the National Research Foundation of Korea funded by the Ministry of Science, ICT & Future Planning (No. 2019H1D3A1A01102643 and 2020R1C1C1008442, 2021M2E7A1079168).

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