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.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project (R01)
Project #
1R01HL121218-01
Application #
8614184
Study Section
Special Emphasis Panel (ZRG1-DTCS-A (81))
Program Officer
Eu, Jerry Pc
Project Start
2014-02-01
Project End
2018-01-31
Budget Start
2014-02-01
Budget End
2015-01-31
Support Year
1
Fiscal Year
2014
Total Cost
$637,177
Indirect Cost
$217,981
Name
Washington University
Department
Surgery
Type
Schools of Medicine
DUNS #
068552207
City
Saint Louis
State
MO
Country
United States
Zip Code
63130
Ibrahim, Mohsen; Wang, Xingan; Puyo, Carlos A et al. (2015) Human recombinant apyrase therapy protects against canine pulmonary ischemia-reperfusion injury. J Heart Lung Transplant 34:247-53
Todd, Jamie L; Wang, Xingan; Sugimoto, Seichiro et al. (2014) Hyaluronan contributes to bronchiolitis obliterans syndrome and stimulates lung allograft rejection through activation of innate immunity. Am J Respir Crit Care Med 189:556-66