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

Abstract

Immune checkpoint inhibitors (ICIs) are widely used in cancer immunotherapy, requiring effective methods for response monitoring. This study evaluated changes in F-18-2-fluoro-2-deoxy-D-glucose (FDG) and F-18-fluorothymidine (FLT) uptake by tumors following ICI treatment as potential imaging biomarkers in mice. Tumor uptakes of F-18-FDG and F-18-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, F-18-FDG uptake was higher in the treatment group, whereas F-18-FLT uptake was not different. There was no difference in F-18-FDG uptake between the two groups in the late phase. However, F-18-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 F-18-FLT, whereas F-18-FDG showed altered metabolism in both tumor and immune cells. A combination of F-18-FLT and F-18-FDG PET, such as GTR, is expected to serve as a potentially effective imaging biomarker for monitoring ICI treatment.