The characterization of 18F-hGTS13 for molecular imaging of xC- transporter activity with positron emission tomography

The aim of this study was development of an improved PET radiotracer for measuring xC (-) activity with increased tumor uptake and reduced uptake in inflammatory cells compared with (S)-4-(3-(18)F-fluoropropyl)-l-glutamate ((18)F-FSPG). Methods: A racemic glutamate derivative, (18)F-hGTS13, was evaluated in cell culture and animal tumor models. (18)F-hGTS13 was separated into C5 epimers, and the corresponding (18)F-hGTS13-isomer1 and (18)F-hGTS13-isomer2 were evaluated in H460 tumor-bearing rats. Preliminary studies investigated the cellular uptake of (18)F-hGTS13-isomer2 in multiple immune cell populations and states. Results: (18)F-hGTS13 demonstrated excellent H460 tumor visualization with high tumor-to-background ratios, confirmed by ex vivo biodistribution studies. Tumor-associated radioactivity was significantly higher for (18)F-hGTS13 (7.5 +/- 0.9 percentage injected dose [%ID]/g, n = 3) than for (18)F-FSPG (4.6 +/- 0.7 %ID/g, n = 3, P = 0.01). (18)F-hGTS13-isomer2 exhibited excellent H460 tumor visualization (6.3 +/- 1.1 %ID/g, n = 3) and significantly reduced uptake in multiple immune cell populations relative to (18)F-FSPG. (18)F-hGTS13-isomer2 exhibited increased liver uptake relative to (18)F-FSPG (4.6 +/- 0.8 vs. 0.7 +/- 0.01 %ID/g), limiting its application in hepatocellular carcinoma. Conclusion: (18)F-hGTS13-isomer2 is a new PET radiotracer for molecular imaging of xC (-) activity that may provide information on tumor oxidation states. (18)F-hGTS13-isomer2 has potential for clinical translation for imaging cancers of the thorax because of the low background signal in healthy tissue.