chapter  62
18 Pages

In Vivo Bioluminescence Imaging as a Tool for Drug Development

ByChristopher H. Contag and Pamela R. Contag ..............................................................................62-1

Animal models that are used for biological assessment in drug development typically represent advanced, or even end-stage, disease and often require sacrifice of the animal for analysis. The assays that are subsequently performed on tissue samples can be time-consuming and can only provide a snapshot of the overall disease course, even when performed on large numbers of animals. Therefore, one must consider the limitations of the data that result from conventional animal protocols that employ

ex vivo

assays, which are constrained by sample size, limited to a small number of selected time points, and performed in the absence of intact organ systems. Moreover, in the current paradigm of target-directed drug discovery, the events that occur early in the disease process represent important targets for therapeutic intervention, and therefore development of assays that provide access to information about these targets during therapeutic intervention is essential for evaluating the new classes of compounds that are being developed. Functional imaging that is relatively high-throughput and yields multiparameter data

will be required to sort out the vast numbers of targets and compounds introduced into drug discovery by this evolving paradigm. Imaging strategies have been designed specifically for laboratory animals, and their use for

in vivo

assessment of therapeutic efficacy has the potential to greatly influence the pharmaceutical industry. One of these imaging modalities,

in vivo

bioluminescent imaging (BLI), and its application to drug discovery and drug development are the subject of this chapter.