Imaging drug delivery and drug responses in the lung

Abstract

Conventional two-dimensional and three-dimensional single photon emission computed tomography and positron emission tomography imaging tools and specific inhaled radiotracers allow accurate and reliable measurements of drug delivery to the lung. Pharmacokinetics and patterns of drug distribution can be monitored over time. In addition, physiologic measurements of ventilation, perfusion, mucociliary clearance, inflammation, and respiratory absorption can be determined using imaging; the results correlate with "black-box" outcomes (for example, spirometry, airway responsiveness, and inflammatory markers in sputum, and bronchoalveolar lavage fluid), providing an indication of the disease state in situ and the effectiveness of therapeutic and other interventions on these critical lung functions. Imaging is widely used in drug discovery. Screening of new drugs using animal models and specifically molecular imaging before human studies is an approach used extensively by the pharmaceutical industry. Topical drug delivery to the lung remains the route of choice for administering respiratory therapies; recently, inhaled therapies have been formulated to gain access to the systemic circulation via the distal lung. Imaging provides a means of validating drug delivery to the site of action in the lung and of measuring the resulting pharmacokinetics of these therapies. No other tool or test provides this type of visual detail supported by numerical information related to a specific drug molecule.