Anti PD-1 treatment increases [18F]FDG uptake by cancer cells in a mouse B16F10 melanoma model

Mayu Tomita; Hironobu Yasui; Kei Higashikawa; Kohei Nakajima; Hideo Takakura; Tohru Shiga; Yuji Kuge; Mikako Ogawa

doi:10.1186/s13550-018-0433-1

Anti PD-1 treatment increases [¹⁸F]FDG uptake by cancer cells in a mouse B16F10 melanoma model

EJNMMI Res. 2018 Aug 16;8(1):82. doi: 10.1186/s13550-018-0433-1.

Authors

Mayu Tomita¹, Hironobu Yasui², Kei Higashikawa², Kohei Nakajima¹, Hideo Takakura¹, Tohru Shiga³, Yuji Kuge², Mikako Ogawa⁴

Affiliations

¹ Laboratory of Bioanalysis and Molecular Imaging, Graduate School of Pharmaceutical Sciences, Hokkaido University, Sapporo, Hokkaido, 060-0812, Japan.
² Central Institute of Isotope Science, Hokkaido University, Sapporo, Japan.
³ Graduate School of Medicine, Hokkaido University, Sapporo, Japan.
⁴ Laboratory of Bioanalysis and Molecular Imaging, Graduate School of Pharmaceutical Sciences, Hokkaido University, Sapporo, Hokkaido, 060-0812, Japan. mogawa@pharm.hokudai.ac.jp.

Abstract

Background: Programmed cell death 1 (PD-1) inhibitors act as immune checkpoint inhibitors and are more effective for improving survival time with less toxicity as compared with conventional chemotherapies. In anti PD-1 therapy, it is important to evaluate metabolism in the cancer microenvironment, as this helps to clarify the pathological conditions. Herein, we investigate the early effects of PD-1 therapy on 2-deoxy-2-[¹⁸F]fluoro-D-glucose ([¹⁸F]FDG) uptake in vivo, focusing on cell distribution and glycolysis in both cancer and immune cells.

Results: In a B16F10 melanoma model, [¹⁸F]FDG-positron emission tomography (PET) was performed before treatment and 7 days after the start of treatment. Values were calculated as the percentage-injected activity per gram of tissue (%IA/g). Flow-cytometry was then performed to assess immune cell populations and glucose metabolism. There was a negligible difference in [¹⁸F]FDG uptake between tumors in the treatment group and non-treatment group before the treatment. In contrast, mean [¹⁸F]FDG uptake in the treatment group tumors was significantly higher (8.06 ± 0.48 %IA/g; P = 0.0074) than that in the non-treatment group (4.02 ± 1.03 %IA/g) after anti PD-1 treatment. Assessment of tumor immune cell populations showed that treatment slightly enriched CD8⁺ T cells and CD4⁺ T cells; however, infiltration of immune cells was negligible, and thus, immune cells were not responsible for the increase in [¹⁸F]FDG uptake. On the other hand, anti PD-1 treatment significantly increased glucose transporter 1 (GLUT1) and hexokinase II expression in CD45^- cancer cells, indicating that anti PD-1 treatment increased glucose metabolism in cancer cells.

Conclusion: The present study shows that anti PD-1 therapy increases glucose metabolism in cancer cells.

Keywords: Immune checkpoint inhibitor; Mouse melanoma; PD-1; Tumor microenvironment; [18F]FDG.