Molecular imaging of the TGF-β activating integrin αvβ6 detects chronic lung allograft dysfunction

Marlene Cano; Chandra S. Bathula; Fuyi Liao; Cristian Wieczorek Villas Boas; Yan Tao; Zhiyi Liu; Ricky Ebenezer; Victoria Davis; Allison Cannady; Dequan Zhou; Shunning Liang; Hanqiu Zhao; Derek E. Byers; Alexander S. Krupnick; Daniel Kreisel; Susan M. Lin; Allen Duong; Tereza Martinu; Zhiyu Dai; Buck E. Rogers; Andrew E. Gelman

doi:10.1172/jci.insight.204555

¹Department of Medicine, Division of Pulmonology & Critical Care Medicine, Washington University School of Medicine, St. Louis, United States of America

²Department of Radiation Oncology, Washington University School of Medicine, St. Louis, United States of America

³Department of Surgery, Division of Cardiothoracic Surgery, Washington University School of Medicine, St. Louis, United States of America

⁴Department of Surgery, University of Maryland School of Medicine, Baltimore, United States of America

⁵Department of Medicine, Division of Pulmonology & Critical Care Medicine, Washington University in Saint Louis, St. Louis, United States of America

⁶Toronto Lung Transplant Program, Ajmera Transplant Center, University Health Network, Toronto, Canada

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¹Department of Medicine, Division of Pulmonology & Critical Care Medicine, Washington University School of Medicine, St. Louis, United States of America

²Department of Radiation Oncology, Washington University School of Medicine, St. Louis, United States of America

³Department of Surgery, Division of Cardiothoracic Surgery, Washington University School of Medicine, St. Louis, United States of America

⁴Department of Surgery, University of Maryland School of Medicine, Baltimore, United States of America

⁵Department of Medicine, Division of Pulmonology & Critical Care Medicine, Washington University in Saint Louis, St. Louis, United States of America

⁶Toronto Lung Transplant Program, Ajmera Transplant Center, University Health Network, Toronto, Canada

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¹Department of Medicine, Division of Pulmonology & Critical Care Medicine, Washington University School of Medicine, St. Louis, United States of America

²Department of Radiation Oncology, Washington University School of Medicine, St. Louis, United States of America

³Department of Surgery, Division of Cardiothoracic Surgery, Washington University School of Medicine, St. Louis, United States of America

⁴Department of Surgery, University of Maryland School of Medicine, Baltimore, United States of America

⁵Department of Medicine, Division of Pulmonology & Critical Care Medicine, Washington University in Saint Louis, St. Louis, United States of America

⁶Toronto Lung Transplant Program, Ajmera Transplant Center, University Health Network, Toronto, Canada

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¹Department of Medicine, Division of Pulmonology & Critical Care Medicine, Washington University School of Medicine, St. Louis, United States of America

²Department of Radiation Oncology, Washington University School of Medicine, St. Louis, United States of America

³Department of Surgery, Division of Cardiothoracic Surgery, Washington University School of Medicine, St. Louis, United States of America

⁴Department of Surgery, University of Maryland School of Medicine, Baltimore, United States of America

⁵Department of Medicine, Division of Pulmonology & Critical Care Medicine, Washington University in Saint Louis, St. Louis, United States of America

⁶Toronto Lung Transplant Program, Ajmera Transplant Center, University Health Network, Toronto, Canada

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¹Department of Medicine, Division of Pulmonology & Critical Care Medicine, Washington University School of Medicine, St. Louis, United States of America

²Department of Radiation Oncology, Washington University School of Medicine, St. Louis, United States of America

³Department of Surgery, Division of Cardiothoracic Surgery, Washington University School of Medicine, St. Louis, United States of America

⁴Department of Surgery, University of Maryland School of Medicine, Baltimore, United States of America

⁵Department of Medicine, Division of Pulmonology & Critical Care Medicine, Washington University in Saint Louis, St. Louis, United States of America

⁶Toronto Lung Transplant Program, Ajmera Transplant Center, University Health Network, Toronto, Canada

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¹Department of Medicine, Division of Pulmonology & Critical Care Medicine, Washington University School of Medicine, St. Louis, United States of America

²Department of Radiation Oncology, Washington University School of Medicine, St. Louis, United States of America

³Department of Surgery, Division of Cardiothoracic Surgery, Washington University School of Medicine, St. Louis, United States of America

⁴Department of Surgery, University of Maryland School of Medicine, Baltimore, United States of America

⁵Department of Medicine, Division of Pulmonology & Critical Care Medicine, Washington University in Saint Louis, St. Louis, United States of America

⁶Toronto Lung Transplant Program, Ajmera Transplant Center, University Health Network, Toronto, Canada

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¹Department of Medicine, Division of Pulmonology & Critical Care Medicine, Washington University School of Medicine, St. Louis, United States of America

²Department of Radiation Oncology, Washington University School of Medicine, St. Louis, United States of America

³Department of Surgery, Division of Cardiothoracic Surgery, Washington University School of Medicine, St. Louis, United States of America

⁴Department of Surgery, University of Maryland School of Medicine, Baltimore, United States of America

⁵Department of Medicine, Division of Pulmonology & Critical Care Medicine, Washington University in Saint Louis, St. Louis, United States of America

⁶Toronto Lung Transplant Program, Ajmera Transplant Center, University Health Network, Toronto, Canada

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¹Department of Medicine, Division of Pulmonology & Critical Care Medicine, Washington University School of Medicine, St. Louis, United States of America

²Department of Radiation Oncology, Washington University School of Medicine, St. Louis, United States of America

³Department of Surgery, Division of Cardiothoracic Surgery, Washington University School of Medicine, St. Louis, United States of America

⁴Department of Surgery, University of Maryland School of Medicine, Baltimore, United States of America

⁵Department of Medicine, Division of Pulmonology & Critical Care Medicine, Washington University in Saint Louis, St. Louis, United States of America

⁶Toronto Lung Transplant Program, Ajmera Transplant Center, University Health Network, Toronto, Canada

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¹Department of Medicine, Division of Pulmonology & Critical Care Medicine, Washington University School of Medicine, St. Louis, United States of America

²Department of Radiation Oncology, Washington University School of Medicine, St. Louis, United States of America

³Department of Surgery, Division of Cardiothoracic Surgery, Washington University School of Medicine, St. Louis, United States of America

⁴Department of Surgery, University of Maryland School of Medicine, Baltimore, United States of America

⁵Department of Medicine, Division of Pulmonology & Critical Care Medicine, Washington University in Saint Louis, St. Louis, United States of America

⁶Toronto Lung Transplant Program, Ajmera Transplant Center, University Health Network, Toronto, Canada

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¹Department of Medicine, Division of Pulmonology & Critical Care Medicine, Washington University School of Medicine, St. Louis, United States of America

²Department of Radiation Oncology, Washington University School of Medicine, St. Louis, United States of America

³Department of Surgery, Division of Cardiothoracic Surgery, Washington University School of Medicine, St. Louis, United States of America

⁴Department of Surgery, University of Maryland School of Medicine, Baltimore, United States of America

⁵Department of Medicine, Division of Pulmonology & Critical Care Medicine, Washington University in Saint Louis, St. Louis, United States of America

⁶Toronto Lung Transplant Program, Ajmera Transplant Center, University Health Network, Toronto, Canada

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¹Department of Medicine, Division of Pulmonology & Critical Care Medicine, Washington University School of Medicine, St. Louis, United States of America

²Department of Radiation Oncology, Washington University School of Medicine, St. Louis, United States of America

³Department of Surgery, Division of Cardiothoracic Surgery, Washington University School of Medicine, St. Louis, United States of America

⁴Department of Surgery, University of Maryland School of Medicine, Baltimore, United States of America

⁵Department of Medicine, Division of Pulmonology & Critical Care Medicine, Washington University in Saint Louis, St. Louis, United States of America

⁶Toronto Lung Transplant Program, Ajmera Transplant Center, University Health Network, Toronto, Canada

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¹Department of Medicine, Division of Pulmonology & Critical Care Medicine, Washington University School of Medicine, St. Louis, United States of America

²Department of Radiation Oncology, Washington University School of Medicine, St. Louis, United States of America

³Department of Surgery, Division of Cardiothoracic Surgery, Washington University School of Medicine, St. Louis, United States of America

⁴Department of Surgery, University of Maryland School of Medicine, Baltimore, United States of America

⁵Department of Medicine, Division of Pulmonology & Critical Care Medicine, Washington University in Saint Louis, St. Louis, United States of America

⁶Toronto Lung Transplant Program, Ajmera Transplant Center, University Health Network, Toronto, Canada

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¹Department of Medicine, Division of Pulmonology & Critical Care Medicine, Washington University School of Medicine, St. Louis, United States of America

²Department of Radiation Oncology, Washington University School of Medicine, St. Louis, United States of America

³Department of Surgery, Division of Cardiothoracic Surgery, Washington University School of Medicine, St. Louis, United States of America

⁴Department of Surgery, University of Maryland School of Medicine, Baltimore, United States of America

⁵Department of Medicine, Division of Pulmonology & Critical Care Medicine, Washington University in Saint Louis, St. Louis, United States of America

⁶Toronto Lung Transplant Program, Ajmera Transplant Center, University Health Network, Toronto, Canada

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¹Department of Medicine, Division of Pulmonology & Critical Care Medicine, Washington University School of Medicine, St. Louis, United States of America

²Department of Radiation Oncology, Washington University School of Medicine, St. Louis, United States of America

³Department of Surgery, Division of Cardiothoracic Surgery, Washington University School of Medicine, St. Louis, United States of America

⁴Department of Surgery, University of Maryland School of Medicine, Baltimore, United States of America

⁵Department of Medicine, Division of Pulmonology & Critical Care Medicine, Washington University in Saint Louis, St. Louis, United States of America

⁶Toronto Lung Transplant Program, Ajmera Transplant Center, University Health Network, Toronto, Canada

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¹Department of Medicine, Division of Pulmonology & Critical Care Medicine, Washington University School of Medicine, St. Louis, United States of America

²Department of Radiation Oncology, Washington University School of Medicine, St. Louis, United States of America

³Department of Surgery, Division of Cardiothoracic Surgery, Washington University School of Medicine, St. Louis, United States of America

⁴Department of Surgery, University of Maryland School of Medicine, Baltimore, United States of America

⁵Department of Medicine, Division of Pulmonology & Critical Care Medicine, Washington University in Saint Louis, St. Louis, United States of America

⁶Toronto Lung Transplant Program, Ajmera Transplant Center, University Health Network, Toronto, Canada

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¹Department of Medicine, Division of Pulmonology & Critical Care Medicine, Washington University School of Medicine, St. Louis, United States of America

²Department of Radiation Oncology, Washington University School of Medicine, St. Louis, United States of America

³Department of Surgery, Division of Cardiothoracic Surgery, Washington University School of Medicine, St. Louis, United States of America

⁴Department of Surgery, University of Maryland School of Medicine, Baltimore, United States of America

⁵Department of Medicine, Division of Pulmonology & Critical Care Medicine, Washington University in Saint Louis, St. Louis, United States of America

⁶Toronto Lung Transplant Program, Ajmera Transplant Center, University Health Network, Toronto, Canada

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¹Department of Medicine, Division of Pulmonology & Critical Care Medicine, Washington University School of Medicine, St. Louis, United States of America

²Department of Radiation Oncology, Washington University School of Medicine, St. Louis, United States of America

³Department of Surgery, Division of Cardiothoracic Surgery, Washington University School of Medicine, St. Louis, United States of America

⁴Department of Surgery, University of Maryland School of Medicine, Baltimore, United States of America

⁵Department of Medicine, Division of Pulmonology & Critical Care Medicine, Washington University in Saint Louis, St. Louis, United States of America

⁶Toronto Lung Transplant Program, Ajmera Transplant Center, University Health Network, Toronto, Canada

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¹Department of Medicine, Division of Pulmonology & Critical Care Medicine, Washington University School of Medicine, St. Louis, United States of America

²Department of Radiation Oncology, Washington University School of Medicine, St. Louis, United States of America

³Department of Surgery, Division of Cardiothoracic Surgery, Washington University School of Medicine, St. Louis, United States of America

⁴Department of Surgery, University of Maryland School of Medicine, Baltimore, United States of America

⁵Department of Medicine, Division of Pulmonology & Critical Care Medicine, Washington University in Saint Louis, St. Louis, United States of America

⁶Toronto Lung Transplant Program, Ajmera Transplant Center, University Health Network, Toronto, Canada

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¹Department of Medicine, Division of Pulmonology & Critical Care Medicine, Washington University School of Medicine, St. Louis, United States of America

²Department of Radiation Oncology, Washington University School of Medicine, St. Louis, United States of America

³Department of Surgery, Division of Cardiothoracic Surgery, Washington University School of Medicine, St. Louis, United States of America

⁴Department of Surgery, University of Maryland School of Medicine, Baltimore, United States of America

⁵Department of Medicine, Division of Pulmonology & Critical Care Medicine, Washington University in Saint Louis, St. Louis, United States of America

⁶Toronto Lung Transplant Program, Ajmera Transplant Center, University Health Network, Toronto, Canada

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¹Department of Medicine, Division of Pulmonology & Critical Care Medicine, Washington University School of Medicine, St. Louis, United States of America

²Department of Radiation Oncology, Washington University School of Medicine, St. Louis, United States of America

³Department of Surgery, Division of Cardiothoracic Surgery, Washington University School of Medicine, St. Louis, United States of America

⁴Department of Surgery, University of Maryland School of Medicine, Baltimore, United States of America

⁵Department of Medicine, Division of Pulmonology & Critical Care Medicine, Washington University in Saint Louis, St. Louis, United States of America

⁶Toronto Lung Transplant Program, Ajmera Transplant Center, University Health Network, Toronto, Canada

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¹Department of Medicine, Division of Pulmonology & Critical Care Medicine, Washington University School of Medicine, St. Louis, United States of America

²Department of Radiation Oncology, Washington University School of Medicine, St. Louis, United States of America

³Department of Surgery, Division of Cardiothoracic Surgery, Washington University School of Medicine, St. Louis, United States of America

⁴Department of Surgery, University of Maryland School of Medicine, Baltimore, United States of America

⁵Department of Medicine, Division of Pulmonology & Critical Care Medicine, Washington University in Saint Louis, St. Louis, United States of America

⁶Toronto Lung Transplant Program, Ajmera Transplant Center, University Health Network, Toronto, Canada

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JCI Insight. https://doi.org/10.1172/jci.insight.204555.
Copyright © 2026, Cano et al. This work is licensed under the Creative Commons Attribution 4.0 International License. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.

Published November 10, 2026 - Version history

TGF-β-activating integrins promote solid-organ fibrosis, suggesting their potential as disease markers. Chronic lung allograft dysfunction (CLAD), a progressive fibrotic complication that limits lung transplant survival, is driven by intragraft TGF-β activation. However, TGF-β-activating integrin expression patterns remain undefined in lung transplants. Single-cell RNA sequencing and proteomic analysis of tissue specimens from a mouse CLAD model and human explanted lungs with CLAD revealed high levels of the TGF-β-activating integrin αvβ6, primarily localized to fibrosis-associated Keratin 8⁺ alveolar transitional epithelial cells, which were greatly reduced in tolerant lungs. Molecular imaging with a newly optimized positron emission tomography radiotracer specific for αvβ6, [⁶⁴Cu]Cu-DOTA-A20-K16R, showed significantly higher uptake in CLAD than in tolerant transplants. [⁶⁴Cu]Cu-DOTA-A20-K16R activity was also reduced by experimental treatments that lowered αvβ6 expression and inhibited CLAD severity. Finally, [⁶⁴Cu]Cu-DOTA-A20-K16R autoradiographic analysis of human explanted lungs with CLAD showed elevated activity that correlated with increased αvβ6 expression. Collectively, these findings illustrate the potential utility of αvβ6 molecular imaging for detecting CLAD pathogenesis.

Version 1 (November 10, 2026): In-Press Preview

Molecular imaging of the TGF-β activating integrin αvβ6 detects chronic lung allograft dysfunction

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