FDG-PET Imaging in Young Cystic Fibrosis Patients

Study Overview
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Brief Summary
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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
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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.

Official Title
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FDG-PET Imaging in Young Cystic Fibrosis Patients

Conditions
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Cystic Fibrosis

Intervention / Treatment
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* Diagnostic Test: FDG-PET


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 12 Years
Maximum Age: 21 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Diagnostic
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Interventional Model Description: In this pilot study, we examined the value of FDG-PET scans as a noninvasive measure of neutrophilic inflammation in adolescents and young adults with cystic fibrosis. All subjects underwent scans.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: Stable lung function<br>* 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. | Diagnostic Test: FDG-PET<br>* All subjects underwent FDG-PET and low-dose volumetric CT imaging. After completing a transmission scan, [18F]FDG was injected intravenously at the start of dynamic scan acquisition. Regions of interest were drawn over multiple tomographic slices to determine average whole-lung and regional lung tissue [18F] FDG uptake. Patlak graphical analysis was used to determine the rate of [18F]FDG uptake from the blood input function and lung tissue activity curves, measured as the influx constant Ki (slope of the linear regression from the Patlak plot). Corrected Ki (i.e., Ki divided by the initial volume of distribution). Lung density was calculated from the attenuation image by standard methods.<br>|
| Other: Rapidly deteriorating lung function<br>* 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. | Diagnostic Test: FDG-PET<br>* All subjects underwent FDG-PET and low-dose volumetric CT imaging. After completing a transmission scan, [18F]FDG was injected intravenously at the start of dynamic scan acquisition. Regions of interest were drawn over multiple tomographic slices to determine average whole-lung and regional lung tissue [18F] FDG uptake. Patlak graphical analysis was used to determine the rate of [18F]FDG uptake from the blood input function and lung tissue activity curves, measured as the influx constant Ki (slope of the linear regression from the Patlak plot). Corrected Ki (i.e., Ki divided by the initial volume of distribution). Lung density was calculated from the attenuation image by standard methods.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Kinetic Influx Constant (Ki) | 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. | At the time of FDG scan, 1 to 2 hours | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Sputum Neutrophil Elastase (NE) Concentration | 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 | Sample collected within 2-hours of PET scan |