DOI: 10.1186/s13550-018-0433-1Pages: 1-8

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

1. Hokkaido University, Laboratory of Bioanalysis and Molecular Imaging, Graduate School of Pharmaceutical Sciences

2. Hokkaido University, Central Institute of Isotope Science

3. Hokkaido University, Graduate School of Medicine

Correspondence to:
Mikako Ogawa
Tel: +81-11-706-3767
Email: mogawa@pharm.hokudai.ac.jp

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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.

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  • Accepted: Aug 6, 2018
  • Online: Aug 16, 2018

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