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Sci Rep. 2017 May 15;7(1):1912. doi: 10.1038/s41598-017-02123-2.

A One-Pot Three-Component Double-Click Method for Synthesis of [67Cu]-Labeled Biomolecular Radiotherapeutics.

Author information

1
Biofunctional Synthetic Chemistry Laboratory, RIKEN, 2-1 Hirosawa, Wako, Saitama, 351-0198, Japan.
2
RI Applications Team, RIKEN Nishina Center for Accelerator-Based Science, 2-1 Hirosawa, Wako, Saitama, 351-0198, Japan.
3
The Institute of Medical Science, The University of Tokyo, 4-6-1 Shirokanedai, Minato-ku, Tokyo, 108-8639, Japan.
4
Accelerator Group, RIKEN Nishina Center for Accelerator-Based Science, 2-1 Hirosawa, Wako, Saitama, 351-0198, Japan.
5
Biofunctional Synthetic Chemistry Laboratory, RIKEN, 2-1 Hirosawa, Wako, Saitama, 351-0198, Japan. kotzenori@riken.jp.
6
Biofunctional Chemistry Laboratory, A. Butlerov Institute of Chemistry, Kazan Federal University, 18 Kremlyovskaya street, Kazan, 420008, Russia. kotzenori@riken.jp.
7
JST-PRESTO, Hirosawa, Wako-shi, Saitama, 351-0198, Japan. kotzenori@riken.jp.

Abstract

A one-pot three-component double-click process for preparing tumor-targeting agents for cancer radiotherapy is described here. By utilizing DOTA (or NOTA) containing tetrazines and the TCO-substituted aldehyde, the two click reactions, the tetrazine ligation (an inverse electron-demand Diels-Alder cycloaddition) and the RIKEN click (a rapid 6π-azaelectrocyclization), could simultaneously proceed under mild conditions to afford covalent attachment of the metal chelator DOTA or NOTA to biomolecules such as to albumin and anti-IGSF4 antibody without altering their activities. Subsequently, radiolabeling of DOTA- or NOTA-attached albumin and anti-IGSF4 antibody (an anti-tumor-targeting antibody) with [67Cu], a β--emitting radionuclide, could be achieved in a highly efficient manner via a simple chelation with DOTA proving to be a more superior chelator than NOTA. Our work provides a new and operationally simple method for introducing the [67Cu] isotope even in large quantities to biomolecules, thereby representing an important process for preparations of clinically relevant tumor-targeting agents for radiotherapy.

PMID:
28507297
PMCID:
PMC5432496
DOI:
10.1038/s41598-017-02123-2
[Indexed for MEDLINE]
Free PMC Article

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