Does the ATSM-Cu(II) Biomarker Integrate into the Human Cellular Copper Cycle?

Gulshan R. Walke, Sharon Ruthstein

Research output: Contribution to journalArticlepeer-review

10 Scopus citations

Abstract

Hypoxia is commonly encountered in the tumor microenvironment and drives proliferation, angiogenesis, and resistance to therapy. Imaging of hypoxia is important in many disease states in oncology, cardiology, and neurology. Finding clinically approved imaging biomarkers for hypoxia has proved challenging. Candidate biomarkers have shown low uptake into tumors and low signal to background ratios that adversely affect imaging quality. Copper complexes have been identified as potential biomarkers for hypoxia owing to their redox ability. Active uptake of copper complexes into cells could ensure selectivity and high sensitivity. We explored the reactivity and selectivity of the ATSM-Cu(II) biomarker to proteins that are involved in the copper cycle using electron paramagnetic resonance (EPR) spectroscopy and UV-vis measurements. We show that the affinity of the ATSM-Cu(II) complex to proteins in the copper cycle is low and the cell probably does not actively uptake ATSM-Cu(II).

Original languageEnglish
Pages (from-to)12278-12285
Number of pages8
JournalACS Omega
Volume4
Issue number7
DOIs
StatePublished - 31 Jul 2019

Bibliographical note

Publisher Copyright:
Copyright © 2019 American Chemical Society.

Funding

We gratefully acknowledge support from the European Research Council (ERC-STG 754365) and a Colman-Soref postdoctoral fellowship for G.W. Authors acknowledge Dr. Lada Gevorkyan-Aiapetov and Zena Bishara for their help in Atox1 expression and purification.

FundersFunder number
Horizon 2020 Framework Programme754365
European Research Council

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