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

Katie M. Parkins; Balaji Krishnamachary; Desmond Jacob; Samata M. Kakkad; Meiyappan Solaiyappan; Akhilesh Mishra; Yelena Mironchik; Marie France Penet; Michael T. McMahon; Philipp Knopf; Bernd J. Pichler; Sridhar Nimmagadd; Zaver M. Bhujwalla

doi:10.1148/rycan.220138

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

Katie M. Parkins, Balaji Krishnamachary, Desmond Jacob, Samata M. Kakkad, Meiyappan Solaiyappan, Akhilesh Mishra, Yelena Mironchik, Marie France Penet, Michael T. McMahon, Philipp Knopf, Bernd J. Pichler, Sridhar Nimmagadd, Zaver M. Bhujwalla

Research output: Contribution to journal › Article › peer-review

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, consis-tent 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.

Original language	English (US)
Article number	e220138
Journal	Radiology: Imaging Cancer
Volume	5
Issue number	4
DOIs	https://doi.org/10.1148/rycan.220138
State	Published - Jul 2023

Keywords

Biolu-minescence Imaging
Hypoxia
PD-L1
PET/MRI
Triple-Negative Breast Cancer

ASJC Scopus subject areas

Radiology Nuclear Medicine and imaging
Oncology

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10.1148/rycan.220138

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Parkins, K. M., Krishnamachary, B., Jacob, D., Kakkad, S. M., Solaiyappan, M., Mishra, A., Mironchik, Y., Penet, M. F., McMahon, M. T., Knopf, P., Pichler, B. J., Nimmagadd, S., & Bhujwalla, Z. M. (2023). PET/MRI and Bioluminescent Imaging Identify Hypoxia as a Cause of Programmed Cell Death Ligand 1 Image Heterogeneity. Radiology: Imaging Cancer, 5(4), Article e220138. https://doi.org/10.1148/rycan.220138

Parkins, KM, Krishnamachary, B, Jacob, D, Kakkad, SM, Solaiyappan, M, Mishra, A, Mironchik, Y, Penet, MF , McMahon, MT, Knopf, P, Pichler, BJ, Nimmagadd, S & Bhujwalla, ZM 2023, 'PET/MRI and Bioluminescent Imaging Identify Hypoxia as a Cause of Programmed Cell Death Ligand 1 Image Heterogeneity', Radiology: Imaging Cancer, vol. 5, no. 4, e220138. https://doi.org/10.1148/rycan.220138

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

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, consis-tent 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 = "Biolu-minescence Imaging, Hypoxia, PD-L1, PET/MRI, Triple-Negative Breast Cancer",

author = "Parkins, {Katie M.} and Balaji Krishnamachary and Desmond Jacob and Kakkad, {Samata M.} and Meiyappan Solaiyappan and Akhilesh Mishra and Yelena Mironchik and Penet, {Marie France} and McMahon, {Michael T.} and Philipp Knopf and Pichler, {Bernd J.} and Sridhar Nimmagadd and Bhujwalla, {Zaver M.}",

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year = "2023",

month = jul,

doi = "10.1148/rycan.220138",

language = "English (US)",

volume = "5",

journal = "Radiology: Imaging Cancer",

issn = "2638-616X",

publisher = "Radiological Society of North America Inc.",

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T1 - PET/MRI and Bioluminescent Imaging Identify Hypoxia as a Cause of Programmed Cell Death Ligand 1 Image Heterogeneity

AU - Parkins, Katie M.

AU - Krishnamachary, Balaji

AU - Jacob, Desmond

AU - Kakkad, Samata M.

AU - Solaiyappan, Meiyappan

AU - Mishra, Akhilesh

AU - Mironchik, Yelena

AU - Penet, Marie France

AU - McMahon, Michael T.

AU - Knopf, Philipp

AU - Pichler, Bernd J.

AU - Nimmagadd, Sridhar

AU - Bhujwalla, Zaver M.

N1 - Publisher Copyright: © RSNA, 2023.

PY - 2023/7

Y1 - 2023/7

N2 - 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, consis-tent 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.

AB - 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, consis-tent 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.

KW - Biolu-minescence Imaging

KW - Hypoxia

KW - PD-L1

KW - PET/MRI

KW - Triple-Negative Breast Cancer

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

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