Glucose-Thymidine Ratio as a Metabolism Index Using 18 F-FDG and 18 F-FLT PET Uptake as a Potential Imaging Biomarker for Evaluating Immune Checkpoint Inhibitor Therapy.

Immune checkpoint inhibitors (ICIs) are widely used in cancer immunotherapy, requiring effective methods for response monitoring. This study evaluated changes in 18 F-2-fluoro-2-deoxy-D-glucose (FDG) and 18 F-fluorothymidine (FLT) uptake by tumors following ICI treatment as potential imaging biomarkers in mice. Tumor uptakes of 18 F-FDG and 18 F-FLT were measured and compared between the ICI treatment and control groups. A combined imaging index of glucose-thymidine uptake ratio (GTR) was defined and compared between groups. In the ICI treatment group, tumor growth was effectively inhibited, and higher proportions of immune cells were observed. In the early phase, 18 F-FDG uptake was higher in the treatment group, whereas 18 F-FLT uptake was not different. There was no difference in 18 F-FDG uptake between the two groups in the late phase. However, 18 F-FLT uptake of the control group was markedly increased compared with the ICI treatment group. GTR was consistently higher in the ICI treatment group in the early and late phases. After ICI treatment, changes in tumor cell proliferation were observed with 18 F-FLT, whereas 18 F-FDG showed altered metabolism in both tumor and immune cells. A combination of 18 F-FLT and 18 F-FDG PET, such as GTR, is expected to serve as a potentially effective imaging biomarker for monitoring ICI treatment.