PET/MRI and Bioluminescent Imaging Identify Hypoxia as a Cause of Programmed Cell Death Ligand 1 Image Heterogeneity

Radiol Imaging Cancer. 2023 Jul;5(4):e220138. doi: 10.1148/rycan.220138.

Abstract

Purpose To examine the association between hypoxia and programmed cell death ligand 1 (PD-L1) expression using bioluminescence imaging (BLI) and PET/MRI in a syngeneic mouse model of triple-negative breast cancer (TNBC). Materials and Methods PET/MRI and optical imaging were used to determine the role of hypoxia in altering PD-L1 expression using a syngeneic TNBC model engineered to express luciferase under hypoxia. Results Imaging showed a close spatial association between areas of hypoxia and increased PD-L1 expression in the syngeneic murine (4T1) tumor model. Mouse and human TNBC cells exposed to hypoxia exhibited a significant increase in PD-L1 expression, consistent with the in vivo imaging data. The role of hypoxia in increasing PD-L1 expression was further confirmed by using The Cancer Genome Atlas analyses of different human TNBCs. Conclusion These results have identified the potential role of hypoxia in contributing to PD-L1 heterogeneity in tumors by increasing cancer cell PD-L1 expression. Keywords: Hypoxia, PD-L1, Triple-Negative Breast Cancer, PET/MRI, Bioluminescence Imaging Supplemental material is available for this article. © RSNA, 2023.

Keywords: Bioluminescence Imaging; Hypoxia; PD-L1; PET/MRI; Triple-Negative Breast Cancer.

MeSH terms

  • Animals
  • Apoptosis
  • B7-H1 Antigen / genetics
  • Humans
  • Hypoxia
  • Ligands
  • Magnetic Resonance Imaging
  • Mice
  • Positron-Emission Tomography
  • Triple Negative Breast Neoplasms* / diagnostic imaging
  • Triple Negative Breast Neoplasms* / genetics

Substances

  • B7-H1 Antigen
  • Ligands