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

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 c...

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Published in:Scientific reports 2017-05, Vol.7 (1), p.1912-9, Article 1912
Main Authors: Fujiki, Katsumasa, Yano, Shinya, Ito, Takeshi, Kumagai, Yuki, Murakami, Yoshinori, Kamigaito, Osamu, Haba, Hiromitsu, Tanaka, Katsunori
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631/92/2783
631/92/96
82
82/1
82/58
Albumin
Albumins - chemistry
Antibodies - chemistry
Cancer
Chelation
Click Chemistry - methods
Copper Radioisotopes - chemistry
HEK293 Cells
Humanities and Social Sciences
Humans
Isotope Labeling
Molecular Structure
multidisciplinary
Organometallic Compounds - chemistry
Radiation therapy
Radiopharmaceuticals - chemical synthesis
Radiopharmaceuticals - chemistry
Science
Science (multidisciplinary)
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cited_by cdi_FETCH-LOGICAL-c606t-9b619c27181eb9bd7c7348418b55bf7811cbdde0666590b8c36cb3863a81e1793
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container_title Scientific reports
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creator Fujiki, Katsumasa
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Haba, Hiromitsu
Tanaka, Katsunori
description 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 [ 67 Cu], 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 [ 67 Cu] isotope even in large quantities to biomolecules, thereby representing an important process for preparations of clinically relevant tumor-targeting agents for radiotherapy.
doi_str_mv 10.1038/s41598-017-02123-2
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subjects 631/92/2783
631/92/96
82
82/1
82/58
Albumin
Albumins - chemistry
Antibodies - chemistry
Cancer
Chelation
Click Chemistry - methods
Copper Radioisotopes - chemistry
HEK293 Cells
Humanities and Social Sciences
Humans
Isotope Labeling
Molecular Structure
multidisciplinary
Organometallic Compounds - chemistry
Radiation therapy
Radiopharmaceuticals - chemical synthesis
Radiopharmaceuticals - chemistry
Science
Science (multidisciplinary)
title A One-Pot Three-Component Double-Click Method for Synthesis of [67Cu]-Labeled Biomolecular Radiotherapeutics
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