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.
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.
|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|
|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|
|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|
|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|
|Huang, Howard J; Isakow, Warren; Byers, Derek E et al. (2015) Imaging pulmonary inducible nitric oxide synthase expression with PET. J Nucl Med 56:76-81|
|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|
|Chen, Delphine L; Kinahan, Paul E (2014) Multimodality molecular imaging of the lung. Clin Transl Imaging 2:391-401|