One of the most convenient methods to assess the pattern of distribution of therapeutic aerosols in the lung is by the use of gamma scintigraphy18. This can measure deposition in the lung, oropharynx and stomach. A critical feature for the success of gamma scintigraphy is a meticulously validated radiolabelling process to give confidence that the radiolabel is behaving in a manner which is representative of the system under study. Conventional planar gamma scintigraphy does not allow clear distinction between central and peripheral deposition since there is an overlay of structures e.g. alveoli, small and large airways, which is most marked centrally. Single photon emission computed tomography (SPECT)19 and positron emission tomography, (PET) have the potential to give more detailed data on regional lung deposition as the image they provide is three-dimensional. Currently these techniques are more expensive and employ higher radiation doses, so are less widely used than planar imaging.
The procedures used for planar scintigraphic assessment of deposition are straightforward. The patient is given the appropriate number of doses of labelled formulation containing 1-2 MBq of activity, usually with a specified inhalation technique, and is then imaged with anterior and posterior views for 30 seconds to 1 minute. There is little point in performing kinetic studies of activity decay over longer periods since it is extremely difficult to ensure that the movement of the label in vivo represents a measurement of any useful physiological or formulation behaviour. If simultaneous pharmacokinetic studies are to be performed, the 'charcoal block' technique can be used, in which the subject is given a charcoal suspension drink prior to administration of the formulation. The object of this is to absorb any drug which may be swallowed and absorbed by the normal gastrointestinal route.
In order to facilitate the construction of regions of interest in the images, krypton 81m gas is commonly used to show the total ventilated area of the lungs. This radioactive gas has a half-life of 13 seconds and therefore the subject is imaged while breathing in the gas from a generator. This area can then be compared to the deposition of radiolabel from a test system. The region of interest can be drawn around the whole lung volume, but it is more common to divide the lung into central and peripheral areas, despite the fact that some peripheral areas must overlie the central area due to the viewing projection. The ratio of peripheral to central deposition is usually termed a 'penetration index'.
Studies based on 3-dimensional acquisition such as SPECT are performed in a similar manner but using a much higher (>100 MBq) activity level. Perring and coworkers19 combined this technique with CT imaging of the lungs and used computer-based methods to transform the data to a concentric-shell lung model, and were thus able to provide a much more rigorous analysis of lung penetration. At present however the technique is considerably more specialized than planar imaging, which is used for the majority of routine studies.
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