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- W2969787007 abstract "607 Objectives: We set out to explore [18F]hGTS13 as a novel radiopharmaceutical to measure xC- transporter activity by positron emission tomography (PET) imaging. The xC- transporter is an emerging oncologic target, mediating oxidative stress and providing a growth advantage for a variety of tumors. This study was performed to evaluate the tumor uptake and biodistribution of [18F]hGTS13 compared to [18]FSPG, a previously described xC- transporter substrate. Methods: Synthesis of [18F]hGTS13 was adopted from US2015/0011773. The cellular uptake of [18F]hGTS13 was first evaluated in H460 and A549 lung carcinoma cell lines. Competition studies were performed using known substrates or inhibitors of the xC- transporter, L-cystine, L-glutamate, (S)-4-carboxyphenyglycine (CPG). To further confirm the specificity of [18F]hGTS13 for the xC- transporter, small inhibitory RNA (siRNA) methodology was used to reduce transporter expression in A549 cells. Human peripheral blood mononuclear cells (PBMCs) were derived from freshly obtained buffy coat fractions and T cells isolated using the Naive Pan T cell Isolation Kit. T cells were activated with the T cell activation/expansion kit (Miltenyi Biotec) and radiotracer uptake was performed 48 hours after activation. H460 tumor bearing rats were investigated with [18F]FSPG and [18F]hGTS13 PET/CT imaging. Results: Cell assays with [18F]hGTS13 revealed rapid and extensive uptake in both A549 and H460 human lung carcinoma cells. Uptake values at 60 mins were 21.6 ± 3.6 and 32.1 ± 0.8 %uptake/mg protein in A549 and H460 cells respectively. Transient reduction of xC- transporter expression in A549 cells resulted in a significant reduction in [18F]hGTS13 uptake (p" @default.
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- W2969787007 date "2018-05-01" @default.
- W2969787007 modified "2023-09-24" @default.
- W2969787007 title "The preclinical characterization of [18F]hGTS13 for imaging of xC- transporter activity" @default.
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