Anzeige
Erschienen in:
05.03.2019 | Research Article
Non-invasive Use of Positron Emission Tomography to Monitor Diethyl maleate and Radiation-Induced Changes in System xC− Activity in Breast Cancer
Erschienen in: Molecular Imaging and Biology | Ausgabe 6/2019
Einloggen, um Zugang zu erhaltenAbstract
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.