Imaging Airway Liquid Absorption in Cystic Fibrosis

• Change in absorptive clearance in response to a therapy [ Time Frame: t=0 and 30 days ] [ Designated as safety issue: No ]
  The absorption rate of the small molecule radiopharmaceutical In111-DTPA from the airways will be compared at baseline and after the inhalation of 7% hypertonic saline (performed on day 30.)
• Short-term change in absorptive clearance (repeatability) [ Time Frame: t=0 and 30 days ] [ Designated as safety issue: No ]
  The absorption rate of the small molecule radiopharmaceutical In111-DTPA from the airways will be compared at baseline and at day 30. This will determine the intra-subject repeatability of the technique.
• Longitudinal change in absorptive clearance [ Time Frame: t=0 and 2 years ] [ Designated as safety issue: No ]
  The absorption rate of the small molecule radiopharmaceutical In111-DTPA from the airways will be compared at baseline and at t=2years. This will allow us to determine how absorptive clearance changes with disease development.

The investigators are developing a new nuclear medicine imaging technique for measuring liquid absorption in the airways that can be applied to screen new medications being developed to treat cystic fibrosis (CF). The investigators believe that the absorption of the small molecule radiopharmaceutical Indium 111-DTPA will indicate changes in liquid absorption in the airways and demonstrate whether new CF medications will be effective. In this study the investigators will further develop this technique through testing involving adult and pediatric CF patients and healthy control subjects.

The investigators have recently developed a novel aerosol-based imaging technique to detect changes in liquid absorption in the airways - a central pathophysiological process known to be important in cystic fibrosis (CF) lung disease. This technique may provide a measure of disease severity and indication of therapeutic correction in advance of currently available outcome measures. It involves the simultaneous delivery of two radiopharmaceuticals by inhalation: one an absorbable small-molecule (Indium-111 labeled diethylene triamine pentaacetic acid; In-DTPA) and the other a non-absorbable particle (Technetium 99m labeled sulfur colloid; Tc-SC). The overarching hypothesis is that DTPA absorption provides a quantifiable, non-invasive measurement of airway liquid absorption that (a) is sensitive to CF genotype, (b) uniquely identifies basic disease phenotype and predicts disease severity, and (c) is modulated by therapeutic interventions.

• Drug: Inhaled hypertonic saline (7%)
  single administration
• Other: Absorptive clearance scan
  Subjects will inhale a nebulized mixture of the radiopharmaceuticals Indium 111-DTPA and Technetium 99m-sulfur colloid.

• Experimental: CF adult response
  In the response arm 16 CF adult subjects will perform absorptive clearance scans at baseline, t=30 days, and t=2 years. During the second scan they will inhale 7% hypertonic saline in order to test the response of absorptive clearance to the therapy.
  Interventions:

  • Drug: Inhaled hypertonic saline (7%)
  • Other: Absorptive clearance scan
• Experimental: CF adult repeatability
  In the repeatability arm 16 CF adult subjects will perform absorptive clearance scans at baseline, t=30 days, and t=2 years. Scanning techniques performed at t=0 and t=30 days will be identical and the results will be compared to establish the repeatability of the technique.
  Intervention: Other: Absorptive clearance scan
• Experimental: CF pediatric
  In the pediatric arm 10 CF subjects ages 6-14 will perform absorptive clearance scans at baseline and at t=2 years.
  Intervention: Other: Absorptive clearance scan
• Experimental: Controls adult
  In the adult control arm 10 healthy adult subjects will perform a single absorptive clearance scan.
  Intervention: Other: Absorptive clearance scan

Inclusion Criteria:

• Adult CF arms:

  • subjects 18 years old or older with a diagnosis of cystic fibrosis as determined by sweat test or genotype
  • subjects who are clinically stable as determined by a physician co-investigator.

• Adult healthy control arm:

  • subjects 18 years old or older without a diagnosis of lung disease.

• Pediatric CF arm:

  • subjects 6-14 years with a diagnosis of cystic fibrosis as determined by sweat test or genotype
  • subjects who are clinically stable as determined by the pediatrician co-investigator
  • subjects must have a previously demonstrated ability to perform reproducible pulmonary function testing based on previous clinical visits.
• Females in all groups who are of child-bearing potential will need to have a negative urine pregnancy test.

Exclusion Criteria:

• Adult CF arm:

  • intolerant to hypertonic saline
  • FEV1%p < 40% of predicted
  • nursing mother
  • positive urine pregnancy test or unwilling to test
  • unwilling to stop hypertonic saline therapy for 72 hours prior to each test day
  • cigarette smoker (regular smoking within 6 months of study).

• Adult healthy control arm:

  • FEV1%p < 80% of predicted
  • nursing mother
  • positive urine pregnancy test or unwilling to test
  • cigarette smoker (regular smoking within 6 months of study).

• Pediatric CF arm:

  • FEV1%p < 40% of predicted
  • nursing mother
  • positive urine pregnancy test for females of childbearing potential
  • unable or unwilling to comply with test procedure
  • cigarette smoker (regular smoking within 6 months of study).
  • Subjects unable to lie recumbent without moving for the 80 minute imaging period will be excluded.

• National Institutes of Health (NIH)
• National Heart, Lung, and Blood Institute (NHLBI)