Lung Disease
Conditions
Keywords
acute lung transplant rejection, neutrophilic lung inflammation, positron emission tomography imaging, [18F] fluorodeoxyglucose, [18F] ISO-1
Brief summary
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.
Detailed description
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.
Interventions
DRUG[18F]FDG
10 millicuries (mCi) of \[18F\]FDG will be injected intravenously at the start of a 60-minute dynamic PET scan acquisition
DRUG[18F]ISO-1
8 mCi of \[18F\]ISO-1 will be injected intravenously at the start of a 60-minute dynamic PET scan acquisition
Sponsors
National Heart, Lung, and Blood Institute (NHLBI)
Washington University School of Medicine
Study design
Observational model
COHORT
Time perspective
CROSS_SECTIONAL
Eligibility
Sex/Gender
ALL
Age
19 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Double-lung transplant recipient * Scheduled for bronchoscopy with transbronchial biopsy * Capable of lying still and supine with arms raised above the head within the PET/CT scanner for \ 1.25 hours * Capable of following instructions for breathing protocol during CT portion of PET/CT * Able and willing to give informed consent * BMI \< 35 * Already scheduled to undergo bronchoscopy with bronchoalveolar lavage (BAL) for clinical reasons * Willing to donate a portion of BAL and biopsy specimen for laboratory testing
Exclusion criteria
* Glucose level \> 150 mg/dl at time of \[18F\]FDG PET scan (however, up to 160 mg/dl, with repeat testing showing level is stable or decreasing, is acceptable) * Pregnancy (confirmed by qualitative urine human chorionic gonadotropin (hCG) pregnancy test) * Lactation * Presence of implanted electronic medical device * Enrollment in another research study of an investigational drug * Inability to lie flat with arms raised above the head for 1.5 hours for PET/CT scans or follow breathing protocol instructions for the CT portion of the PET/CT
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Ki, the influx constant that describes the rate of [18F]FDG uptake, in the whole lung | 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 | This outcome measure is assessed from the [18F]ISO-1 PET scan performed on Day 2. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Progesterone receptor membrane component 1 (PGRMC1) staining of biopsy tissues and bronchoalveolar lavage cells | Assessed after the baseline clinical bronchoscopy procedure is performed 3 days prior to FDG PET/CT scan | 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). |
Countries
United States
Outcome results
None listed