In vivo magnetic resonance methods in pharmaceutical research: current status and perspectives.
In the last decade, in vivo MR methods have become established tools in the drug discovery and development process. In this review, several successful and potential applications of MRI and MRS in stroke, rheumatoid and osteo-arthritis, oncology and cardiovascular disorders are dealt with in detail. The versatility of the MR approach, allowing the study of various pathophysiological aspects in these disorders, is emphasized. New indication areas, for the characterization of which MR methods have hardly been used up to now, such as respiratory, gastro-intestinal and skin diseases, are outlined in a subsequent section. A strength of MRI, being a non-invasive imaging modality, is the ability to provide functional, i.e. physiological, readouts. Functional MRI examples discussed are the analysis of heart wall motion, perfusion MRI, tracer uptake and clearance studies, and neuronal activation studies. Functional information may also be derived from experiments using target-specific contrast agents, which will become important tools in future MRI applications. Finally the role of MRI and MRS for characterization of transgenic and knock-out animals, which have become a key technology in modern pharmaceutical research, is discussed. The advantages of MRI and MRS are versatility, allowing a comprehensive characterization of a diseased state and of the drug intervention, and non-invasiveness, which is of relevance from a statistical, economical and animal welfare point of view. Successful applications in drug discovery exploit one or several of these aspects. In addition, the link between preclinical and clinical studies makes in vivo MR methods highly attractive methods for pharmaceutical research.
Core Technologies Area, Novartis Pharma Research, Basel, Switzerland. markus-1.rudin@pharma.novartis.com
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Beckmann
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Porszasz
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Reese
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D000818:Animals; D030801:Animals, Genetically Modified; D001172:Arthritis, Rheumatoid / Q000175:diagnosis; D002561:Cerebrovascular Disorders / Q000175:diagnosis; D002626:Chemistry, Pharmaceutical / Q000379:methods*; D006801:Humans; D008279:Magnetic Resonance Imaging / Q000379:methods*; D009369:Neoplasms / Q000175:diagnosis; D009374:Neoplasms, Experimental / Q000175:diagnosis; D019906:Nuclear Magnetic Resonance, Biomolecular / Q000379:methods*; D010003:Osteoarthritis / Q000175:diagnosis