Scintigraphic Techniques for Measuring In Vivo Deposition

Knowledge of the total and regional drug deposition in the human respiratory tract is often useful in the assessment of respiratory drugs administered by aerosol delivery systems. The deposition studies usually employ a surrogate gamma emitting chemical instead of a directly labeled drug. With appropriate physical distribution of the label, 'drug' deposition can be studied quantitatively by measurement of the emitted radiation. Because of the structural and functional diversity of the respiratory tract, it is desirable to obtain regional information on the deposition. Generally, it is easier to quantitate relative regional drug distribution than to obtain absolute regional doses. The radiolabeled material deposits in complex three-dimensional (3D) structures. 3D images of the distribution of the radiolabel would be therefore more informative. However, longer acquisition times that may be necessary for 3D images could introduce errors due to body movement and clearance. Tissues absorb and scatter radiation; this necessitates corrections for calculation of the deposited dose. Errors in quantitation are minimized by using subjects as their own controls. When properly implemented and interpreted, deposition studies can be a powerful tool in the design and evaluation of aerosol delivery and its relation to therapeutic and toxic effects. I would like to shape the title of my talk into the context of this conference. David Wyatt was talking earlier on about the wise man's castle while I would like to borrow my architectural analogy from Ancient Egypt - the pyramid. I am not sure if the wise men got buried there but they must have built it. My pyramid (Figure 1) has a broad solid scientific base which supports in vivo measurements. Ultimately, we desire to understand the behavior of our aerosols in vivo; I think that it is quite safe to assume that there is a relationship between the in vitro properties, and the deposition and disposition of the deposited material. Furthermore, the initial deposition of the drug and its carrier and their subsequent removal are related to the drug efficacy and to safety. I am going to talk about the intermediate step, the link between the benchtop measurements and the clinical effects: deposition and disposition studies which might connect the in vitro properties to the efficacy and safety of the drug.