using a SPECT (single photon emission computed tomography) camera, thin-section CT of the 
chest, and mucociliary clearance scans as measures of efficacy. 
1.5.1 Perfusion Scans: Macro-aggregated albumin deposits in the first set of capillaries that 
it encounters. Therefore Tc-99m macro-aggregates of albumin, when given by slow intravenous 
injection, can be used to measure regional perfusion. The SPECT camera has greater resolution 
than planar images of the lung (Phipps et.al., 1989) and can provide useful measure of lung 
function in the treated lobe compared to the control lobe. 
1.5.2 Thin-Section CT Scanning: Computed tomography can be used to image segmental and 
sub-segmental bronchi. The pulmonary parenchyma is imaged well, and the technique is 
sensitive to slight changes in parenchymal density. There have been several reports that have 
compared chest radiographs with CT scans in cystic fibrosis, and all have found that CT 
scanning is more sensitive than chest x-ray in mild cases (Hansell and Stricklan, 1989; Santis 
et.al., 1991). Thin-section CT scanning of the lungs can be used to detect improvement in 
mucus plugging or the architecture of the treated lobe. 
1.5.3 Mucociliary Clearance Scans: Aerosolized Tc-99m-pyrophosphate, after standard planar 
imaging, provides an accurate measure the deposition of an aerosol and its rate of clearance from 
the lungs. Although intersubject variability in measured rates of mucociliary clearance are 
reported to be high, intrasubject variability is very small (Wilkey et.al., 1980). Subjects in the 
current study will have baseline measurements of mucociliary clearance in the lobe to be treated, 
as well as the rest of the lung. Following treatment, changes in clearance in the treated lobe will 
be compared with its baseline and with the control lobe. Attention will be paid to the possible 
confounding effects of other medications, such as theophylline, cough clearance, and differences 
in deposition patterns (William D. Bennett, Cystic Fibrosis Foundation Consensus Conference: 
Clinical Outcomes for Evaluation of New Cystic Fibrosis Therapies, 1992). 
Summary of Clinical Aspects of Cystic Fibrosis: Despite continued progress in the diagnosis, 
treatment and assessment of cystic fibrosis, morbidity and mortality from the pulmonary 
complications of the disease remain an enormous burden on patients and their families. The 
present application seeks to utilize somatic cell gene therapy, by transferring the normal CFTR 
allele to respiratory epithelial cells, in hopes of correcting the primary biochemical and 
physiological abnormalities in CF. 
1.6 Genetic Basis for Cystic Fibrosis: Cystic fibrosis is now known to be causally related to 
abnormalities of the gene encoding the Cystic Fibrosis Transmembrane Conductance Regulator 
(CFTR) and more than 200 distinct genetic alterations in the CFTR DNA have been identified 
and associated with a clinical disorder (Kerem et.al., 1989, Riordan et.al., 1989, Lap Chee Tsui, 
International CF conference, 1992). The most common defect is caused by the deletion of a 
nucleotide triplet associated with the loss of phenylalanine residue at position 508 (termed the 
A508 mutation) that accounts for 70% of CF chromosomes and is associated with clinically 
severe cystic fibrosis. The isolation of the gene and the identification of the primary structure 
of the CFTR polypeptide has led to intense efforts to reconstitute the defect by genetic or 
pharmacologic means. 
Recombinant DNA Research, Volume 17 
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