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Noninvasive Brain Imaging for Experimental Medicine in Drug Discovery and Development

Promise and Pitfalls

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Abstract

There is currently increased focus on experimental medicine in drug development. Imaging methods potentially provide highly cost-effective, general approaches for the noninvasive characterisation of disease and pharmacokinetics, pharmacodynamics and drug effects directly in humans in ways that can enable this. The two methods most widely employed now are positron emission tomography (PET) and magnetic resonance imaging (MRI). PET allows the distribution of radiolabelled molecules to be mapped, enabling studies of molecule distribution and tissue metabolism. MRI was initially used primarily to define tissue structure, but a more recent range of functional MRI techniques promise the potential to define pharmacokinetic data over biologically meaningful timescales. With an understanding of the relationship between imaging biomarker changes and clinical outcomes, imaging can be used as a surrogate marker of response even for the later stages of drug development.

There are pitfalls in the application of these methods, which need to be avoided. The two most common are: (i) getting distracted by the technology rather than focusing on the questions that need to be asked; and (ii) the failure to interpret the imaging data in an appropriate disease- and drug-specific fashion. However, with attention to such issues, imaging should prove a powerful facilitating platform for experimental medicine in the future.

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Acknowledgements

Dr Matthews wishes to thank the MRC for research support in the University of Oxford and gratefully acknowledges receipt of an MRC Clinical Research Chair.

The authors have provided no information on sources of funding or on conflicts of interest directly relevant to the content of this review.

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Authors and Affiliations

  1. MRI Modelling, Clinical Imaging Centre, Translational Medicine and Genetics, GlaxoSmithKline, Greenford, UB6 0HE, England

    Brandon Whitcher

  2. Clinical Imaging Centre, Translational Medicine and Genetics, GlaxoSmithKline, Greenford, UB6 0HE, England

    Paul M. Matthews

  3. Department of Clinical Neurology, Centre for Functional Magnetic Resonance Imaging of the Brain, University of Oxford, John Radcliffe Hospital, Oxford, England

    Paul M. Matthews

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Whitcher, B., Matthews, P.M. Noninvasive Brain Imaging for Experimental Medicine in Drug Discovery and Development. Int J Pharm Med 20, 167–175 (2006). https://doi.org/10.2165/00124363-200620030-00003

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