In recent years, in vivo magnetic resonance (MR) methods have become established tools in the drug discovery and development process. In this article, the role of MR imaging (MRI) in the preclinical evaluation of drugs in animal models of diseases is illustrated on the basis of selected examples. The individual sections are devoted to applications of anatomic, physiologic, and "molecular" imaging providing, respectively, structural-morphological, functional, and target-specific information. The impact of these developments upon clinical drug evaluation is also briefly addressed.
MRI IN THE DRUG DISCOVERY/ DEVELOPMENT PROCESSThe rapid advance of imaging techniques such as magnetic resonance imaging (MRI; see Box 1 for abbreviations) has made them indispensable tools in clinical diagnosis. Whereas the drive for method development was clearly given by clinical applications, recently similar approaches became available for experimental studies in research animals as well. The major issues that have to be addressed in animal imaging are the demands for high spatial resolution and the associated issues of improved sensitivity. From a technologic point of view, the status of clinical and animal MRI today can be considered equivalent. It is precisely the link between preclinical and clinical applications that renders MRI so attractive in pharmacologic research. In this review, we illustrate the role of MRI in the preclinical evaluation of drugs in animal models of diseases.Animal models are used in several phases of the drug development process. The first steps are the identification and validation of a potential drug target. Genetically engineered animals are being increasingly used in this early phase. Later in the process, the safety and efficacy of drug candidates are evaluated in animal models of human diseases. Ideally, in order that study paradigms be easily transferable to clinical drug development, questions concerning drug absorption, distribution, efficacy, metabolism, and elimination should be addressed in a noninvasive manner with high sensitivity and spatial resolution.For most drugs, average tissue con-