Noninvasive structural, functional, and molecular imaging in drug development.
Modern drug research is mechanism-based and the development of disease modifying therapies involves the identification of molecular key players in the pathological cascade. Today, noninvasive imaging tools enable the visualization and quantitative assessment of the expression of molecular targets, of their interaction with potential ligands, as well as of the functional consequence of this interaction at a molecular (e.g. activation of signaling cascades), cellular, metabolic, physiological, and morphological level in a temporo-spatially resolved manner. The ability to gather such information from the intact organism with all regulatory processes in place renders imaging highly attractive for the biomedical researcher and for the drug developer in particular. Molecular imaging is potentially capable of providing this information. Today, proof-of-principle has been established that imaging is in fact adding value to the drug discovery and development processes. Numerous studies have used structural and functional imaging readouts to document therapy efficacy, mainly during lead optimization. Similarly, major efforts have been devoted to the development and evaluation of imaging biomarkers that might serve as early readouts for therapy response with the potential of being used in the clinical drug evaluation thereby facilitating translational research. In this contribution, we illustrate the role and potential of imaging in modern drug discovery and development with selected examples. Yet, despite its huge potential the impact of imaging on drug discovery has been modest in the past; potential reasons will be discussed. Nevertheless, noninvasive imaging methods are rapidly evolving and it is beyond doubt that their importance for biomedical research will increase.
Rudin
Markus
M
Institute for Biomedical Engineering, University of Zürich, HIT-E22.4, Wolfgang-Pauli-Strasse 27, CH-8093 Zürich, Switzerland. rudin@biomed.ee.ethz.ch
D000818:Animals; D054316:Biomarkers, Pharmacological; D003287:Contrast Media / Q000494:pharmacology; D003952:Diagnostic Imaging / Q000379:methods*; D016503:Drug Delivery Systems; D015195:Drug Design; D055808:Drug Discovery / Q000379:methods*; D006801:Humans
D054316:Biomarkers, Pharmacological; D003287:Contrast Media