Assessing NOS Uptake With PET Imaging in Lung Inflammation
Condition: Lung Inflammation
MeSH terms: Pneumonia; Inflammation
Study type: Interventional
Phase: Early Phase 1

Summary: 
      The purpose of this study is to learn more about the basic responses of the lungs to
      inflammation using positron emission tomography, or PET, imaging scans of the lungs. PET is a
      machine that detects radiation and generates pictures using a donut-shaped scanner similar in
      appearance to an x-ray "CAT" or computed tomography (CT) scan or an MRI. Inflammation is the
      way our bodies react to irritation or injury, and involves red, warm, and often painful
      swelling of the affected tissue. An enzyme called inducible nitric oxide synthase (iNOS)
      contributes to the development of lung inflammation.
    

Detailed description: 
      The investigators plan to use three radioactive tracers to produce the PET images for
      measuring lung inflammation: [18F](+/-)NOS (the F stands for fluorine and NOS stands for
      Nitric Oxide Synthase, which targets iNOS), O-15 carbon monoxide ([15O]CO), and O-15 water
      ([15O]H2O). The NOS tracer gives information specifically about lung inflammation, while the
      carbon monoxide and water tracers give information about whether the lung inflammation causes
      more blood or water to be retained in the area of lung inflammation.

      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 does not spread from one part of the body to another, and cannot spread to
      another person), and a small area in only one lung will be affected. In order to created this
      state of controlled lung inflammation, the investigators plan to place a small amount of a
      purified bacterial substance called endotoxin into a single small section of the lung using a
      bronchoscope (a long, flexible narrow tube that is passed through the mouth into the airways
      of the lung). This use of endotoxin is considered investigational, and the investigators have
      received permission from the FDA to use endotoxin in this research study.
    

Intervention name(s): Endotoxin (E. coli O:113, Reference Endotoxin); [18F](+/-)NOS
Intervention type(s): Drug; Drug
Intervention description(s): The endotoxin will be reconstituted with sterile water to a final concentration of 2,000 endotoxin units/ml. The dose of 4 ng/kg will be prepared to a final volume of 2 ml and will be administered using a 5F balloon-tipped monitoring catheter inserted via a fiberoptic bronchoscope into the lateral segment of the right middle lobe of the lung on the morning of Day 2.; 7 mCi of [18F](+/-)NOS will be injected intravenously at the start of a 60-minute dynamic PET scan acquisition
Other intervention name(s): Lipopolysaccharide
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Basic Science
Keywords: lung inflammation; positron emission tomography; inducible nitric oxide synthase