PET Imaging of Endotoxin-induced iNOS Activation
|Pneumonia||Drug: Endotoxin (E. coli O:113, Reference Endotoxin) Drug: [18F](+/-)NOS||Phase 1|
|Study Design:||Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Basic Science
|Official Title:||PET Imaging of Endotoxin-induced iNOS Activation in Healthy Volunteers|
- Distribution volume ratio (DVR), determined by Logan plot analysis, in the right middle lobe. [ Time Frame: Change in DVR on post-endotoxin scan (Day 2) from baseline (Day 1). ]
- Bronchoalveolar lavage (BAL) fluid cell counts. [ Time Frame: 24 hours after endotoxin instillation. ]Total nucleated and neutrophil cell counts obtained by BAL after endotoxin instillation.
- Number and percent of iNOS-stained BAL cells. [ Time Frame: 24 hours after endotoxin instillation. ]
|Study Start Date:||December 2010|
|Study Completion Date:||April 2012|
|Primary Completion Date:||April 2012 (Final data collection date for primary outcome measure)|
Experimental: Endotoxin and [18F](+/-)NOS
All volunteers in this study will receive endotoxin in a single segment of the lung to induce mild, self-limited inflammation. They will also be imaged before and after endotoxin instillation with the novel PET tracer F-18 (+/-) NOS
Drug: Endotoxin (E. coli O:113, Reference Endotoxin)
Other Name: LipopolysaccharideDrug: [18F](+/-)NOS
The investigators plan to use [18F](+/-)NOS (the F stands for fluorine and NOS stands for Nitric Oxide Synthase, the name for the investigational radioactive drug that targets iNOS) and positron emission tomography (PET) imaging as a measure of lung inflammation. PET is a machine that detects radiation and generates pictures using a donut shaped scanner similar in appearance to an x-ray "CAT" scan.
In order to show that [18F](+/-)NOS-PET is related to the amount of inflammation, the investigators first need to create a state of controlled lung inflammation that can be measured and quantified. "Controlled lung inflammation" means a reaction in the lungs that is similar to that which occurs during lung infection (increased respiratory secretions, and cough). It is "controlled" because the investigators will not be using anything alive or contagious (it will not spread from one part of your body to another, and cannot spread to another person) and a small area in only one lung will be affected. In order to create this state of controlled lung inflammation, the investigators plan to put a small amount of endotoxin into a single small section of the lung using a bronchoscope (a long, flexible, narrow tube that is passed through the nose or the mouth into the airways of the lung). This use of endotoxin is considered investigational. The investigators have received permission from the FDA to use endotoxin in this research study.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01407796
|United States, Missouri|
|Washington University School of Medicne|
|St. Louis, Missouri, United States, 63110|
|Principal Investigator:||Delphine L. Chen, MD||Washington University School of Medicine|