Article ID Journal Published Year Pages File Type
2529998 Current Opinion in Pharmacology 2011 7 Pages PDF
Abstract

Clinical imaging offers a range of methods for the support of drug development that are able to address major questions related to target validation and molecule biodistribution, target interactions and pharmacodynamics. Here we review recent innovative applications of positron emission tomography (PET) and magnetic resonance imaging (MRI). New approaches to human target validation exploring MRI or PET biomarker changes related to allelic variation at candidate target loci can contribute to human target validation. PET molecular imaging can define molecule biodistribution directly and, if an appropriate, target-specific radioligand is available, be employed in small experimental medicine studies to provide plasma pharmacokinetic–target occupancy data to guide dose selection. An enlarging range of imaging biomarkers for pharmacodynamic studies is enabling imaging experimental medicine studies to assess the potential efficacy of new therapeutic molecules. Integration of these approaches promises improvements in therapeutic molecule differentiation and may contribute in ways that would improve the value proposition for use of a new drug through patient stratification.

► Clinical imaging can support innovative approaches for new drug development. ► MRI or PET biomarker changes with allelic variation contribute to human target validation. ► PET can define biodistribution or relate plasma concentrations to target occupancies for dose selection. ► Quantitative imaging biomarkers also are enabling an ever greater range of pharmacodynamic studies. ► Integrated use of imaging methods can improve drug differentiation and the value of new drugs.

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