Measuring Total and Regional Lung Deposition Using Inhaled Radiotracers
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The delivery of an inhaled drug to the lungs can be measured by adding a gamma-emitting radiotracer to the formulation and using two-dimensional planar imaging or three-dimensional single photon emission computerized tomography (SPECT) to provide detailed information on lung deposition. The isotope most commonly used is the low energy (140 KeV) isotope, 99m technetium. Radiolabeling techniques have been successfully developed for use with nebulizers, pressurized metered dose inhalers (pMDIs), and dry powder inhaler formulations (DPI), and to investigate drug delivery to the respiratory tract for a variety of drug formulations and patient populations. However, for pMDIs and DPIs, the radiotracer is usually only physically associated with, rather than chemically bound, to the drug. Therefore, once deposited, the radiotracer may disassociate from the drug and cannot be used to track its subsequent fate; however, incorporation of a radiotracer directly into the drug molecule can overcome this. By using positron emitters such as 11carbon or 18fluorine it is possible to generate three-dimensional images of the drug in the lung using positron emission tomography (PET) scanning, which has a higher resolution and is more accurate than SPECT. Labeling drugs with PET emitters is more complex as the drug molecule must first be synthesized to contain the radioactive isotope before the drug is formulated for the inhaler. As with gamma-scintigraphy, PET scanning can be used to investigate physiological changes in the lung following therapeutic intervention, but as biological radiotracers are used, functional images (i.e., of the drug's uptake and metabolism) can also be obtained.