PET Imaging of Endotoxin-induced iNOS Activation

The overall purpose of this research is to gain understanding of the basic responses of the lung to inflammation. Inflammation is the way our bodies react to irritation or injury, and involves red, warm, and often painful swelling of the affected tissue. "Acute lung injury" involves a generalized inflammation to the lung that is activated by any of several conditions: infection, trauma, inhalation of toxic substances, etc. When lung injury is severe, not enough oxygen can get into the body; this can lead to the need for mechanical support of breathing (mechanical ventilation), problems with brain, heart or other organ function, and in some cases, death. Inducible nitric oxide synthase (iNOS) contributes to the development of lung inflammation.

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.

lung inflammation, positron emission tomography (PET), fluorodeoxyglucose (FDG), inducible nitric oxide synthase (iNOS), lung anti-inflammatory therapy

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

Inclusion Criteria: Healthy man or woman, any race or ethnicity, age 19 - 44 years old Screening Pulmonary Function Test Screening oxygen saturation by pulse oximetry >97% on room air Capable of lying still and supine within the PET/CT scanner for 1.5 hours Capable of following instructions for breathing protocol during CT portion of PET/CT Able and willing to give informed consent BMI < 35 Exclusion Criteria: Pregnancy (confirmed by qualitative serum hCG pregnancy test) Lactation Active menstruation History of cardiopulmonary disease Currently taking any prescription medications History of tobacco use or illicit drug use within the past year Presence of implanted electronic medical device Enrollment in another research study of an investigational drug Known allergy to both trimethoprim/sulfamethoxazole and amoxicillin Known allergy to drugs routinely used during bronchoscopy Inability lie flat for 1.5 hours for PET/CT scans or follow breathing protocol instructions for the CT portion of the PET/CT

Huang HJ, Isakow W, Byers DE, Engle JT, Griffin EA, Kemp D, Brody SL, Gropler RJ, Miller JP, Chu W, Zhou D, Pierce RA, Castro M, Mach RH, Chen DL. Imaging pulmonary inducible nitric oxide synthase expression with PET. J Nucl Med. 2015 Jan;56(1):76-81. doi: 10.2967/jnumed.114.146381. Epub 2014 Dec 18.