ABSTRACT
The measurement of lung deposition of inhaled therapeutics and its
interpretation has been debated within the field of inhaled drug delivery
science for many years. Historically, two-dimensional gamma scintigraphy
(planar imaging) has been used to demonstrate total and regional lung
deposition of drugs inhaled from selected aerosol delivery systems [1-4].
Efforts have been made to link total lung deposition with the clinical parameters
of efficacy and safety, though with limited success. Acquisition of 2D
scintigraphic data can be confounded by several factors, such as poor
radiolabeling of the study drug, use of inaccurate tissue attenuation factors
applied when calculating absolute amounts of radioactivity in the lung,
oropharynx, and gut, and poor delineation of the edge of the lung, leading to
incorrectly defined lung regions. In addition, factors influencing the inhalation
of the radiolabeled aerosols may not be well controlled, producing variability in
deposition patterns. Intraindividual variability in data outcomes may result from
a lack of adherence to inclusion/exclusion criteria for study subjects or the
enrollment of subjects with too broad a range of disease severities. Furthermore,
for deposition protocols with concurrent pharmacokinetic measurements,
acquisition of imaging data may be constrained by the need to image
immediately following inhalation of the labeled drug and to precisely measure
plasma drug levels at the same time and, therefore, possibly requiring correction
factors to be applied to the data for any discrepancy in time between the two
sets of measurements.
