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PET/MRI and Bioluminescent Imaging Identify Hypoxia as a Cause of Programmed Cell Death Ligand 1 Image Heterogeneity
Katie M Parkins1, Balaji Krishnamachary1, Desmond Jacob1
1From the Russell H. Morgan Department of Radiology and Radiological Science (K.M.P., B.K., D.J., S.M.K., M.S., A.M., Y.M., M.F.P., M.T.M., S.N., Z.M.B.), Sidney Kimmel Comprehensive Cancer Center (M.F.P., S.N., Z.M.B.), and Department of Radiation Oncology and Molecular Radiation Sciences (Z.M.B.), The Johns Hopkins University School of Medicine, 720 Rutland Ave, Rm 208C Traylor Building, Baltimore, MD 21205; The F.M. Kirby Research Center for Functional Brain Imaging, Kennedy Krieger Institute, Baltimore, Md (M.T.M.); and Werner Siemens Imaging Center, Department of Preclinical Imaging and Radiopharmacy, Eberhard Karls University Tuebingen, Tuebingen, Germany (P.K., B.J.P.).
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.
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