Key Points
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Imaging technologies exploit the interaction of various forms of energy with tissues to non-invasively visualize the body.
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Many imaging techniques were originally developed for human use, but have recently been scaled-down to allow the high-resolution imaging of mice. This is highly relevant, because as genomics provides us with better animal models of disease, imaging readouts can be used to evaluate novel therapeutics.
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Imaging methods offer several advantages over other current practices in drug discovery, examples of which are discussed in this article:
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The use of imaging endpoints instead of time-consuming dissection and histology can significantly decrease the workload involved in tissue analysis and thereby speed up the evaluation of drug candidates.
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Imaging can provide biomarkers of a disease process and thus help to define stratified study groups.
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As imaging methods are non-invasive, they allow for longitudinal studies in a single animal. This increases the statistical relevance of a study, allows for more clinically relevant study designs and decreases the number of animals required.
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Imaging can also provide important information on the optimal timing and dosing of drugs.
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Emerging molecular-imaging tools can provide much earlier surrogate markers of therapy success than is currently possible.
Abstract
Imaging sciences have grown exponentially during the past three decades, and many techniques, such as magnetic resonance imaging, nuclear tomographic imaging and X-ray computed tomography, have become indispensable in clinical use. Advances in imaging technologies and imaging probes for humans and for small animals are now extending the applications of imaging further into drug discovery and development, and have the potential to considerably accelerate the process. This review summarizes some of the recent developments in conventional and molecular imaging, and highlights their impact on drug discovery.
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Academy of Molecular Imaging (AMI)
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Glossary
- MAGNETIC RESONANCE IMAGING
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(MRI). A powerful diagnostic imaging method that uses radiowaves in the presence of a magnetic field to extract information from certain atomic nuclei (most commonly hydrogen). It is primarily used for producing anatomical images, but also gives information on the physico-chemical state of tissues, flow, diffusion, motion and, more recently, molecular targets.
- X-RAY COMPUTED TOMOGRAPHY
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(CT). As generated X-rays pass through different types of tissue, they are deflected or absorbed to different degrees. CT uses X-rays to obtain three-dimensional images by rotating an X-ray source around the subject and measuring the intensity of transmitted X-rays from different angles.
- POSITRON EMISSION TOMOGRAPHY
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(PET). A tomographic imaging technique that detects nuclides as they decay by positron emission.
- SEROTONIN SYSTEM
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This is an important neurotransmission network involved in aggressive and sexual behaviour, depression, anxiety, the sleep–wake cycle, moods, thermoregulation and other functions.
- FLUORESCENCE-MEDIATED TOMOGRAPHY
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A tomographic reconstruction method developed for in vivo imaging of fluorescent probes. Images of deep structures are mathematically reconstructed by solving diffusion equations, under the assumption that photons have been scattered many times.
- FLUORESCENCE REFLECTANCE IMAGING
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A simple method of image acquisition similar to fluorescence microscopy, except that different optics allow image acquisition of whole animals. Mostly suited for surface tumours or surgically exposed tumours.
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Rudin, M., Weissleder, R. Molecular imaging in drug discovery and development. Nat Rev Drug Discov 2, 123–131 (2003). https://doi.org/10.1038/nrd1007
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DOI: https://doi.org/10.1038/nrd1007
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