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Photoactivatable bis(thiosemicarbazone) derivatives for copper-64 radiotracer synthesis

Earley, Daniel F; Esteban Flores, Jose; Guillou, Amaury; Holland, Jason P (2022). Photoactivatable bis(thiosemicarbazone) derivatives for copper-64 radiotracer synthesis. Dalton Transactions, 51(13):5041-5052.

Abstract

In recent years, copper-64 and copper-67 have been considered as a useful theranostic pair in nuclear medicine, due to their favourable and complementary decay properties. As $^{67}Cu$ and $^{64}Cu$ are chemically identical, development of both existing and new bifunctional chelators for $^{64}Cu$ imaging agents can be readily adapted for the $^{67}Cu$-radionuclide. In this study, we explored the use of photoactivatable copper chelators based on the asymmetric bis(thiosemicarbazone) scaffold, H$_2$ATSM/en, for the photoradiolabelling of protein. Photoactivatable $^{64}$CuATSM-derivatives were prepared by both direct synthesis and transmetallation from the corresponding $^{nat}$Zn complex. Then, irradiation with UV light in the presence of a protein of interest in a pH buffered aqueous solution afforded the $^{64}Cu$-labelled protein conjugates in decay-corrected radiochemical yield of 86.9 ± 1.0% via the transmetallation method and 35.3 ± 1.7% from the direct radiolabelling method. This study successfully demonstrates the viability of photochemically induced conjugation methods for the development of copper-based radiotracers for potential applications in diagnostic positron emission tomography (PET) imaging and targeted radionuclide therapy.

Additional indexing

Item Type:Journal Article, refereed, original work
Communities & Collections:07 Faculty of Science > Department of Chemistry
Dewey Decimal Classification:540 Chemistry
Scopus Subject Areas:Physical Sciences > Inorganic Chemistry
Uncontrolled Keywords:Inorganic Chemistry
Language:English
Date:1 January 2022
Deposited On:05 Jan 2023 09:05
Last Modified:28 Oct 2024 02:40
Publisher:Royal Society of Chemistry
ISSN:1477-9226
OA Status:Hybrid
Free access at:PubMed ID. An embargo period may apply.
Publisher DOI:https://doi.org/10.1039/d2dt00209d
PubMed ID:35285835
Project Information:
  • Funder: H2020
  • Grant ID: 101001734
  • Project Title: PhotoPHARMA - Light-induced synthesis of protein-drug conjugates for imaging and therapy
  • Funder: H2020
  • Grant ID: 676904
  • Project Title: Developing multi-modality nanomedicines for targeted annotation of oncogenic signaling pathways
  • Funder: Swiss National Science Foundation
  • Grant ID: PP00P2_163683
  • Project Title:
  • Funder: Swiss National Science Foundation
  • Grant ID: PP00P2_190093
  • Project Title:
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  • Licence: Creative Commons: Attribution-NonCommercial 4.0 International (CC BY-NC 4.0)
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  • Content: Accepted Version
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