The purpose of this research study is to gain understanding of the basic responses of the lungs to inflammation and specifically if there may be a better way to detect graft inflammation using non-invasive methods as well as to determine the effectiveness of immunosuppressive treatment regimens in preventing acute rejection in lung transplant recipients.
Positron emission tomography with fluorodeoxyglucose (FDG-PET) is a potential way we can measure lung inflammation. FDG-PET imaging is a clinically accepted and FDA-approved method that is commonly used in the diagnosis and management of cancer. PET is a machine that detects radiation and generates pictures using a donut shaped scanner similar in appearance to an x-ray "CAT" computerized axial tomography or computed tomography (CT) scan. FDG stands for \[18F\] (flourine 18) fluorodeoxyglucose, a radiolabeled sugar that is used to identify areas of inflammation with the PET scanner. A CT scan takes a picture of what the lungs and airways look like. T cells are the primary cause of acute rejection of lung transplants. Because T cells must divide in order to be activated and cause rejection, imaging them while they are dividing is another way that we can determine whether acute rejection is occurring. A new PET tracer called \[18F\]ISO-1 (18F-labeled σ2-receptor ligand for PET, N-(4-(6,7-dimethoxy-3,-4-dihydroisoquinolin-2(1H)-yl)butyl)-2-(2-18F-fluoroethoxy)-5-methylbenzamide (18F-3c), binds to dividing cells. Therefore, \[18F\]ISO-1 may help us measure acute rejection more accurately. \[18F\]ISO-1 is an investigational drug.
Study Type
OBSERVATIONAL
Enrollment
28
10 millicuries (mCi) of \[18F\]FDG will be injected intravenously at the start of a 60-minute dynamic PET scan acquisition
8 mCi of \[18F\]ISO-1 will be injected intravenously at the start of a 60-minute dynamic PET scan acquisition
Washington University School of Medicine / Barnes-Jewish Hospital
St Louis, Missouri, United States
Ki, the influx constant that describes the rate of [18F]FDG uptake, in the whole lung
Time frame: This outcome measure is assessed from the [18F]FDG scan performed on Day 1.
Logan plot analysis determined distribution volume ratio (DVR) of [18F] ISO-1 uptake
Time frame: This outcome measure is assessed from the [18F]ISO-1 PET scan performed on Day 2.
Progesterone receptor membrane component 1 (PGRMC1) staining of biopsy tissues and bronchoalveolar lavage cells
The biopsy specimens will be stained for proliferation markers. The bronchoalveolar lavage cells will be assessed for glucose uptake with 2-NBDG ( fluorescent glucose analog that has been used to monitor glucose uptake in live cells, as an indicator of cell viability).
Time frame: Assessed after the baseline clinical bronchoscopy procedure is performed 3 days prior to FDG PET/CT scan
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