A Flexible Synthesis of (68)Ga-Labeled Carbonic Anhydrase IX (CAIX)-Targeted Molecules via CBT/1,2-Aminothiol Click Reaction

We herein describe a flexible synthesis of a small library of (68)Ga-labeled CAIX-targeted molecules via an orthogonal 2-cyanobenzothiazole (CBT)/1,2-aminothiol click reaction. Three novel CBT-functionalized chelators (1–3) were successfully synthesized and labeled with the positron emitter gallium-...

Descripción completa

Detalles Bibliográficos
Autores principales: Chen, Kuo-Ting, Nguyen, Kevin, Ieritano, Christian, Gao, Feng, Seimbille, Yann
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2018
Materias:
Article
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6337199/
https://www.ncbi.nlm.nih.gov/pubmed/30577607
http://dx.doi.org/10.3390/molecules24010023
_version_ 1783388190294409216
author Chen, Kuo-Ting
Nguyen, Kevin
Ieritano, Christian
Gao, Feng
Seimbille, Yann
author_facet Chen, Kuo-Ting
Nguyen, Kevin
Ieritano, Christian
Gao, Feng
Seimbille, Yann
author_sort Chen, Kuo-Ting
collection PubMed
description We herein describe a flexible synthesis of a small library of (68)Ga-labeled CAIX-targeted molecules via an orthogonal 2-cyanobenzothiazole (CBT)/1,2-aminothiol click reaction. Three novel CBT-functionalized chelators (1–3) were successfully synthesized and labeled with the positron emitter gallium-68. Cross-ligation between the pre-labeled bifunctional chelators (BFCs) and the 1,2-aminothiol-acetazolamide derivatives (8 and 9) yielded six new (68)Ga-labeled CAIX ligands with high radiochemical yields. The click reaction conditions were optimized to improve the reaction rate for applications with short half-life radionuclides. Overall, our methodology allows for a simple and efficient radiosynthetic route to produce a variety of (68)Ga-labeled imaging agents for tumor hypoxia.
format Online
Article
Text
id pubmed-6337199
institution National Center for Biotechnology Information
language English
publishDate 2018
publisher MDPI
record_format MEDLINE/PubMed
spelling pubmed-63371992019-01-25 A Flexible Synthesis of (68)Ga-Labeled Carbonic Anhydrase IX (CAIX)-Targeted Molecules via CBT/1,2-Aminothiol Click Reaction Chen, Kuo-Ting Nguyen, Kevin Ieritano, Christian Gao, Feng Seimbille, Yann Molecules Article We herein describe a flexible synthesis of a small library of (68)Ga-labeled CAIX-targeted molecules via an orthogonal 2-cyanobenzothiazole (CBT)/1,2-aminothiol click reaction. Three novel CBT-functionalized chelators (1–3) were successfully synthesized and labeled with the positron emitter gallium-68. Cross-ligation between the pre-labeled bifunctional chelators (BFCs) and the 1,2-aminothiol-acetazolamide derivatives (8 and 9) yielded six new (68)Ga-labeled CAIX ligands with high radiochemical yields. The click reaction conditions were optimized to improve the reaction rate for applications with short half-life radionuclides. Overall, our methodology allows for a simple and efficient radiosynthetic route to produce a variety of (68)Ga-labeled imaging agents for tumor hypoxia. MDPI 2018-12-21 /pmc/articles/PMC6337199/ /pubmed/30577607 http://dx.doi.org/10.3390/molecules24010023 Text en © 2018 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Chen, Kuo-Ting
Nguyen, Kevin
Ieritano, Christian
Gao, Feng
Seimbille, Yann
A Flexible Synthesis of (68)Ga-Labeled Carbonic Anhydrase IX (CAIX)-Targeted Molecules via CBT/1,2-Aminothiol Click Reaction
title A Flexible Synthesis of (68)Ga-Labeled Carbonic Anhydrase IX (CAIX)-Targeted Molecules via CBT/1,2-Aminothiol Click Reaction
title_full A Flexible Synthesis of (68)Ga-Labeled Carbonic Anhydrase IX (CAIX)-Targeted Molecules via CBT/1,2-Aminothiol Click Reaction
title_fullStr A Flexible Synthesis of (68)Ga-Labeled Carbonic Anhydrase IX (CAIX)-Targeted Molecules via CBT/1,2-Aminothiol Click Reaction
title_full_unstemmed A Flexible Synthesis of (68)Ga-Labeled Carbonic Anhydrase IX (CAIX)-Targeted Molecules via CBT/1,2-Aminothiol Click Reaction
title_short A Flexible Synthesis of (68)Ga-Labeled Carbonic Anhydrase IX (CAIX)-Targeted Molecules via CBT/1,2-Aminothiol Click Reaction
title_sort flexible synthesis of (68)ga-labeled carbonic anhydrase ix (caix)-targeted molecules via cbt/1,2-aminothiol click reaction
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6337199/
https://www.ncbi.nlm.nih.gov/pubmed/30577607
http://dx.doi.org/10.3390/molecules24010023
work_keys_str_mv AT chenkuoting aflexiblesynthesisof68galabeledcarbonicanhydraseixcaixtargetedmoleculesviacbt12aminothiolclickreaction
AT nguyenkevin aflexiblesynthesisof68galabeledcarbonicanhydraseixcaixtargetedmoleculesviacbt12aminothiolclickreaction
AT ieritanochristian aflexiblesynthesisof68galabeledcarbonicanhydraseixcaixtargetedmoleculesviacbt12aminothiolclickreaction
AT gaofeng aflexiblesynthesisof68galabeledcarbonicanhydraseixcaixtargetedmoleculesviacbt12aminothiolclickreaction
AT seimbilleyann aflexiblesynthesisof68galabeledcarbonicanhydraseixcaixtargetedmoleculesviacbt12aminothiolclickreaction
AT chenkuoting flexiblesynthesisof68galabeledcarbonicanhydraseixcaixtargetedmoleculesviacbt12aminothiolclickreaction
AT nguyenkevin flexiblesynthesisof68galabeledcarbonicanhydraseixcaixtargetedmoleculesviacbt12aminothiolclickreaction
AT ieritanochristian flexiblesynthesisof68galabeledcarbonicanhydraseixcaixtargetedmoleculesviacbt12aminothiolclickreaction
AT gaofeng flexiblesynthesisof68galabeledcarbonicanhydraseixcaixtargetedmoleculesviacbt12aminothiolclickreaction
AT seimbilleyann flexiblesynthesisof68galabeledcarbonicanhydraseixcaixtargetedmoleculesviacbt12aminothiolclickreaction

Ejemplares similares