FDG-PET Imaging in Young Cystic Fibrosis Patients

Not Applicable

Completed

Brief Summary: The purpose of this research is to determine how a person's lungs will uptake \[18F\]fluorodeoxyglucose (FDG), as measured with positron emission tomography (PET) scanning in young cystic fibrosis (CF) patients.

Detailed Description: Our recent study in CF adults, supplemented by recent pre-clinical and clinical studies by our group suggests that labeled fluorodeoxyglocose-based positron emission tomography (FDG-PET) imaging may be a valuable quantitative biomarker of lung inflammation. The proposed study would validate our earlier findings, but in a younger patient population. The implications of such a test could be highly significant for both the testing of promising new anti-inflammatory agents and for patient management decisions. To capitalize on this exciting opportunity, the critical next step is to show that we can identify a cohort of young CF patients with both stable lung function and normal (or near normal) FDG-PET imaging studies. Similar patients, then, would become the subjects for a future prospective cohort study to determine if FDG-PET imaging can in fact serve as a predictor of future changes in lung function.

Recruitment & Eligibility

Inclusion Criteria

Confirmed diagnosis of cystic fibrosis
Age 12 to 21 years old, of either gender, any race or ethnicity
Stable recent pulmonary status (defined as no new pulmonary symptoms, new antibiotic use, or hospitalization for pulmonary symptoms for at least 1 month).
We will permit patients treated with the macrolide antibiotic, azithromycin, to participate in this study. Azithromycin has recently become a virtual standard of care in CF, based on small but reproducible improvements in pulmonary function over 4 months of treatment with this drug. The mechanism of benefit is uncertain, but an anti-inflammatory effect has been suggested. The high prevalence of use means that a study without azithromycin would likely require a wash-out period, without data about the appropriate duration for such a wash-out, or whether inflammatory markers would reverse during that time.

Exclusion Criteria

Failure to obtain informed consent
Positive pregnancy test or lactation
Currently enrolled in another study involving radioisotopes or an investigational drug
Recent (within 30 days of screening) hospitalization for any reason
New antibiotic use (within 30 days of screening).
Patient incapable of lying still and supine within the PET/computed X-ray tomography (CT) scanner for 90 minutes.
Patient incapable of completing other testing procedures (e.g., PFT, induced sputum)
Patient with serum glucose greater than 150 mg/dl at time of PET imaging study
Patient incapable of fasting for 4 to 6 hrs prior to PET imaging study

Arm && Interventions

Group	Intervention	Description
Rapidly deteriorating lung function	FDG-PET	\* Group R (n = 14) will contain CF patients, aged 12-21 years old, who underwent FDG-PET with rapidly deteriorating lung function during the past 4 years with greater than 4% per year decline. There is no therapeutic intervention and FDG-PET scan will be performed in both cohorts.
Stable lung function	FDG-PET	\* Group S (n = 14) will consist of CF patients, aged 12-21 years old, who underwent FDG-PET with stable lung function during the past 4 years, defined as less than 2% decline per year. There is no therapeutic intervention and FDG-PET scan will be performed in both cohorts.

Primary Outcome Measures

Name	Time	Method
Kinetic Influx Constant (Ki)	At the time of FDG scan, 1 to 2 hours	The whole lung kinetic influx constant (Ki) is the primary outcome measure that is derived from the time-activity curves, which are generated from regions of interest placed over the whole lungs. Therefore, a single time-activity curves from each scan is used to derive the Ki.

Secondary Outcome Measures

Name	Time	Method
Sputum Neutrophil Elastase (NE) Concentration	Sample collected within 2-hours of PET scan	Using established techniques, functional activity of neutrophil elastase in sputum sols were measured using methoxy-succinyl-ala-ala-pro-val-nitroanilide (Elastin Products, Owensville, MO), specific peptide chromogenic substrates of the neutrophil protease