Lung transplantation is the treatment of choice for end-stage lung disease, but survival after lung transplant remains disappointingly low. Acute rejection episodes put lung grafts at greater risk of failing. However, acute rejection is often clinically silent and difficult to detect by any means other than biopsy, which requires an invasive procedure. Therefore, noninvasive methods for detecting and quantifying the presence of acute rejection could potentially improve outcomes for lung transplant recipients by improving our ability to detect acute rejection that requires treatment. Because T cells must proliferate in the lungs to cause acute rejection, we propose using the novel positron emission tomography (PET) tracer [18F]ISO-1, which targets the proliferation marker sigma-2 receptor, also recently characterized as the progesterone receptor membrane component-1 (PGRMC1), to image T cell activation in lung grafts. We have shown that PET imaging with [18F]fluorodeoxyglucose ([18F]FDG) also detects acute rejection and can measure its response to treatment; therefore, we will evaluate the ability of [18F]ISO-1 and [18F]FDG to detect acute rejection in a novel mouse model of left lung transplantation and in human lung transplant recipients.

Public Health Relevance

This proposal develops new imaging techniques for detecting and quantifying acute lung transplant rejection. Lung transplantation is frequently the last option for end-stage lung disease, but survival remains poor. Investigators will be able to use these imaging techniques to better identify lung transplant recipients who need more intensive immunosuppression and determine whether their treatment is effective to reduce the risk of lung transplant failure.

National Institute of Health (NIH)
National Heart, Lung, and Blood Institute (NHLBI)
Research Project (R01)
Project #
Application #
Study Section
Special Emphasis Panel (ZRG1-DTCS-A (81)S)
Program Officer
Reineck, Lora A
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
Washington University
Schools of Medicine
Saint Louis
United States
Zip Code
Scozzi, Davide; Wang, Xingan; Liao, Fuyi et al. (2018) Neutrophil extracellular trap fragments stimulate innate immune responses that prevent lung transplant tolerance. Am J Transplant :
Ibrahim, Mohsen; Scozzi, Davide; Toth, Kelsey A et al. (2018) Naive CD4+ T Cells Carrying a TLR2 Agonist Overcome TGF-?-Mediated Tumor Immune Evasion. J Immunol 200:847-856
Chen, Delphine L; Schiebler, Mark L; Goo, Jin Mo et al. (2017) PET imaging approaches for inflammatory lung diseases: Current concepts and future directions. Eur J Radiol 86:371-376
Gelman, Andrew E; Fisher, Andrew J; Huang, Howard J et al. (2017) Report of the ISHLT Working Group on Primary Lung Graft Dysfunction Part III: Mechanisms: A 2016 Consensus Group Statement of the International Society for Heart and Lung Transplantation. J Heart Lung Transplant 36:1114-1120
Puyo, Carlos A; Peruzzi, Daniela; Earhart, Alexander et al. (2017) Endotracheal tube-induced sore throat pain and inflammation is coupled to the release of mitochondrial DNA. Mol Pain 13:1744806917731696
Chen, Delphine L; Cheriyan, Joseph; Chilvers, Edwin R et al. (2017) Quantification of Lung PET Images: Challenges and Opportunities. J Nucl Med 58:201-207
Onyema, Oscar Okwudiri; Guo, Yizhan; Wang, Qing et al. (2017) Eosinophils promote inducible NOS-mediated lung allograft acceptance. JCI Insight 2:
Michel, Loren S; Dyroff, Samantha; Brooks, Frank J et al. (2017) PET of Poly (ADP-Ribose) Polymerase Activity in Cancer: Preclinical Assessment and First In-Human Studies. Radiology 282:453-463
Scozzi, Davide; Ibrahim, Mohsen; Menna, Cecilia et al. (2017) The Role of Neutrophils in Transplanted Organs. Am J Transplant 17:328-335
Liu, Y; Li, W; Luehmann, H P et al. (2016) Noninvasive Imaging of CCR2+ Cells in Ischemia-Reperfusion Injury After Lung Transplantation. Am J Transplant 16:3016-3023

Showing the most recent 10 out of 14 publications