PET imaging-based evaluation of aerosol drugs and their delivery devices: nasal and pulmonary studies

Three-dimensional (3-D) positron emission tomography (PET) imaging of inhaled radiolabeled aerosol in the nasal or pulmonary regions provides an in vivo measurement of drug distribution using the drug itself as the tracer. Repeated or dynamic PET scans over the time after inhalation provides us with further information about the fate of the deposited drug. These quantitative measurements are sufficient to describe the performance of a drug or device and they are obtained in a noninvasive fashion, which cannot be achieved by using any other methods. Using this PET-imaging paradigm, we conducted a sequence of drug studies to evaluate the performance of aerosol drugs and delivery devices; to compare the performance of similar drugs from different manufacturers; to assess the similarity between different formulations and propellants for the same drug; to appraise delivery devices such as spacers and nebulizers, etc. This paper reviews only the imaging and data analysis techniques developed for the above-mentioned studies that include multi-modality image registration, region definition and region-based data analysis, and nonregion-based data analysis. We separated the techniques into nasal and pulmonary studies because of the uniqueness of each group. Specific drugs or devices are not identified and no result about drug performance is given because the imaging and data analysis methodology, which is the focus of this paper, applies to all these studies regardless of the drugs or their delivery devices. The quantitative data are used as the scientific basis for evaluation although we also developed visualization techniques to enhance the results drawn from the data.