The use of small animal imaging in respiratory disease drug discovery

The expansion of scientific knowledge and technology over the past decades did not result in an increased rate of drug discoveries for respiratory diseases. Despite the identification of numerous targets and lead compounds, few new therapeutic molecules have reached patient care. It is generally acknowledged that the large cost of drug development is mainly because of the high failure rate during clinical testing. Animal models of respiratory disorders used for experimental proof-of-principle and efficacy studies are often criticized because of inherent limitations, one of them being the tool-box used for the assessment of outcomes. Noninvasive imaging is a novel approach which might help to reverse this trend. Different imaging modalities can be combined and molecular, functional and anatomical events can be assessed quantitatively. Compounds with potential beneficial effects can be radiolabeled and proof-of-principle experiments can be addressed to ensure that the drug meets the area with pathology at sufficient concentrations. This method will also help to further characterize different animal models of respiratory disease calling researchers attention to the inherent limitations of each respective model, thus preventing subsequent futile use. Furthermore, preclinical trials can be performed longitudinally in animals in which the pathology has been quantitatively assessed before drug administration. The obvious benefit from a drug discovery perspective is that this approach is a vigorous test for any new drug or indication and probably will facilitate more ‘earlier and better failures’. This review is focusing on multiple components of assessing respiratory diseases with noninvasive small animal imaging tools and how they can be adapted for drug discovery.