RT Journal Article
SR Electronic
T1 The Characterization of <sup>18</sup>F-hGTS13 for Molecular Imaging of x<sub>C</sub><sup>−</sup> Transporter Activity with PET
JF Journal of Nuclear Medicine
JO J Nucl Med
FD Society of Nuclear Medicine
SP 1812
OP 1817
DO 10.2967/jnumed.119.225870
VO 60
IS 12
A1 Corinne Beinat
A1 Gayatri Gowrishankar
A1 Bin Shen
A1 Israt S. Alam
A1 Elise Robinson
A1 Tom Haywood
A1 Chirag B. Patel
A1 Emily Carmen Azevedo
A1 Jessa B. Castillo
A1 Ohad Ilovich
A1 Norman Koglin
A1 Heribert Schmitt-Willich
A1 Mathias Berndt
A1 Andre Mueller
A1 Marion Zerna
A1 Ananth Srinivasan
A1 Sanjiv Sam Gambhir
YR 2019
UL http://jnm.snmjournals.org/content/60/12/1812.abstract
AB 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-(3-18F-fluoropropyl)-l-glutamate (18F-FSPG). Methods: A racemic glutamate derivative, 18F-hGTS13, was evaluated in cell culture and animal tumor models. 18F-hGTS13 was separated into C5 epimers, and the corresponding 18F-hGTS13-isomer1 and 18F-hGTS13-isomer2 were evaluated in H460 tumor–bearing rats. Preliminary studies investigated the cellular uptake of 18F-hGTS13-isomer2 in multiple immune cell populations and states. Results: 18F-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 18F-hGTS13 (7.5 ± 0.9 percentage injected dose [%ID]/g, n = 3) than for 18F-FSPG (4.6 ± 0.7 %ID/g, n = 3, P = 0.01). 18F-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 18F-FSPG. 18F-hGTS13-isomer2 exhibited increased liver uptake relative to 18F-FSPG (4.6 ± 0.8 vs. 0.7 ± 0.01 %ID/g), limiting its application in hepatocellular carcinoma. Conclusion: 18F-hGTS13-isomer2 is a new PET radiotracer for molecular imaging of xC− activity that may provide information on tumor oxidation states. 18F-hGTS13-isomer2 has potential for clinical translation for imaging cancers of the thorax because of the low background signal in healthy tissue.