Non-invasive Use of Positron Emission Tomography to Monitor Diethyl maleate and Radiation-Induced Changes in System xC− Activity in Breast Cancer View Full Text


Ontology type: schema:ScholarlyArticle     


Article Info

DATE

2019-03-05

AUTHORS

Milena Čolović, Hua Yang, Helen Merkens, Nadine Colpo, François Bénard, Paul Schaffer

ABSTRACT

PURPOSE: The system xC- transporter is upregulated in cancer cells in response to oxidative stress (OS). 5-[18F]fluoroaminosuberic acid ([18F]FASu) has been reported as a novel positron emission tomography (PET) imaging agent, targeting system xC-. The goal of this study was to evaluate the utility of [18F]FASu in monitoring cellular response to diethyl maleate (DEM) and radiation-induced OS fluctuations. PROCEDURES: [18F]FASu uptake by breast cancer cells was studied in correlation to OS biomarkers: glutathione (GSH) and reactive oxygen species (ROS), as well as transcriptional and translational levels of xCT (the functional subunit of xC-). System xC- inhibitor, sulfasalazine (SSZ), and small interfering RNA (siRNA) knockdown were used as negative controls. Radiotracer uptake was evaluated in three breast cancer models: MDA-MB-231, MCF-7, and ZR-75-1, at two-time points (1 h and 16 h) following OS induction. In vivo [18F]FASu imaging and biodistribution were performed using MDA-MB-231 xenograft-bearing mice at 16 and 24 h post-radiation treatment. RESULTS: [18F]FASu uptake was positively correlated to intracellular GSH and SLC7A11 expression levels, and radiotracer uptake was induced both by radiation treatment and by DEM at time points longer than 3 h. In an in vivo setting, there was no statistically significant uptake difference between irradiated and control tumors. CONCLUSION: [18F]FASu is a specific system xC- PET radiotracer and as such it can be used to monitor system xC- activity due to OS. As such, [18F]FASu has the potential to be used in therapy response monitoring by PET. Further optimization is required for in vivo application. More... »

PAGES

1-10

Identifiers

URI

http://scigraph.springernature.com/pub.10.1007/s11307-019-01331-8

DOI

http://dx.doi.org/10.1007/s11307-019-01331-8

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1112540962

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/30838549


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