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 Beinat, Corinne
A1 Gowrishankar, Gayatri
A1 Shen, Bin
A1 Alam, Israt S.
A1 Robinson, Elise
A1 Haywood, Tom
A1 Patel, Chirag B.
A1 Azevedo, Emily Carmen
A1 Castillo, Jessa B.
A1 Ilovich, Ohad
A1 Koglin, Norman
A1 Schmitt-Willich, Heribert
A1 Berndt, Mathias
A1 Mueller, Andre
A1 Zerna, Marion
A1 Srinivasan, Ananth
A1 Gambhir, Sanjiv Sam
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.