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Non-invasive Use of Positron Emission Tomography to Monitor Diethyl Maleate and Radiation-Induced Changes in System X

Non-invasive Use of Positron Emission Tomography to Monitor Diethyl Maleate and Radiation-Induced Changes in System X

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

Mol Imaging Biol. 2019 Dec;21(6):1107-1116.

PMID: 30838549

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.

Chemicals Related in the Paper:

Catalog Number	Product Name	Structure	CAS Number	Price
AP141059	Diethyl maleate		141-05-9	Price

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