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.

A View on Imaging in Drug Research and Development for Respiratory Diseases

“…Determining the topical dose and distribution of inhaled therapies can be accomplished using radiolabeled tracers and imaging. The most widely used techniques in humans (Dolovich and Labiris, 2004) and small animals (Merkel et al, 2009) use two-dimensional planar ␥-cameras and 3D SPECT cameras. It is important that there is no significant change in the in vitro performance of the …”

In vivo animal models for drug delivery across the lung mucosal barrier☆

“…PET is a 3D functional imaging technique that provides accurate information on dose, distribution and kinetics of an inhaled radiotracer in the lungs [159]. This technique used to assess drug delivery to animals would provide a wealth of additional information including more accurate images detailing the regional distribution of the drug in the lungs, in vivo estimation of large airway/small airway deposition and functional imaging of physiologic and biologic processes in vivo [160]. The major advantage of PET is its high sensitivity without the penetration limitations of optical techniques.…”

Depósito pulmonar de partículas inhaladas

“…La gammagrafía proporciona imáge-nes planas del pulmón, es decir, en 2 dimensiones (2D), y se ha empleado frecuentemente para comparar la eficiencia del depósito pulmonar de aerosoles empleando distintos dispositivos de inhalación, así como los efectos de diferentes parámetros respiratorios y de la enfermedad pulmonar sobre el depósito. La distribución del fármaco por lo general se estudia según zonas de interés, es decir, comparando la región apical con la basal, o una distribución central con la periférica 76 .…”