18F-5-Fluoroaminosuberic Acid as a Potential Tracer to Gauge Oxidative Stress in Breast Cancer Models

• DOI: 10.2967/jnumed.116.180661
• Publication Date: 2016-10-28T01:59:55Z
• Authors: Hua Yang; Silvia Jenni; Milena Colovic; Helen Merkens; Carlee Poleschuk; Isabel Rodrigo; Qing Miao; Bruce F. Johnson; Michael J. Rishel; Vesna Sossi; Jack M. Webster; François Bénard; Paul Schaffer
• Keywords: Amino Acid Transport System y+; Reproducibility of Results; Breast Neoplasms; Sensitivity and Specificity; Antioxidants; Amino Acids, Dicarboxylic; 3. Good health; Oxidative Stress; 03 medical and health sciences; 0302 clinical medicine; Cell Line, Tumor; Positron-Emission Tomography; Feasibility Studies; Humans; Radiopharmaceuticals

The cystine transporter (system x_C⁻) is an antiporter of and glutamate. It has relatively low basal expression in most tissues becomes upregulated cells under oxidative stress (OS) as one the genes expressed response to antioxidant element promoter. We have developed ¹⁸F-5-fluoroaminosuberic acid (FASu), a PET tracer that targets system x_C⁻. goal this study was evaluate ¹⁸F-FASu specific gauge for x_C⁻ activity vivo its potential breast cancer imaging. <b>Methods:</b>¹⁸F-FASu specificity toward studied by cell inhibition assay, cellular uptake after OS induction with diethyl maleate, without anti-xCT small interfering RNA knockdown, vitro studies, x_C⁻–transduced xenograft model. In addition, radiotracer evaluated 3 models: MDA-MB-231, MCF-7, ZR-75-1. <b>Results:</b> Reactive oxygen species–inducing maleate increased glutathione levels uptake, whereas gene knockdown led decreased uptake. robustly inhibited inhibitors or substrates, significantly higher transduced tumors expressing xCT than wild-type HEK293T (<i>P</i> &lt; 0.0001 cells, <i>P</i> = 0.0086 tumors). demonstrated tumor all lines studied. Among them, triple-negative which highest messenger level, had 0.0058 when compared MCF-7; ZR-75-1). <b>Conclusion:</b>¹⁸F-FASu substrate functional monitoring By enabling noninvasive analysis responses vivo, biomarker may serve valuable target diagnosis treatment certain cancers.