Abstract
Targeted drugs hold great promise for the treatment of malignant tumors; however, there are several challenges for efficient evaluation of these drugs in preclinical and clinical studies. These challenges include identifying the 'correct', biologically active concentration and dose schedule, selecting the patients likely to benefit from treatment, monitoring inhibition of the target protein or pathway, and assessing the response of the tumor to therapy. Although anatomic imaging will remain important, molecular imaging provides several new opportunities to make the process of drug development more efficient. Various techniques for molecular imaging that enable noninvasive and quantitative imaging are now available in the preclinical and clinical settings, to aid development and evaluation of new drugs for the treatment of cancer. In this Review, we discuss the integration of molecular imaging into the process of drug development and how molecular imaging can address key questions in the preclinical and clinical evaluation of new targeted drugs. Examples include imaging of the expression and inhibition of drug targets, noninvasive tissue pharmacokinetics, and early assessment of the tumor response.
Key Points
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There is an urgent need to develop and use assays that accelerate the drug development and evaluation processes and, at the same time, reduce the drugs' costs
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Radiolabeled drug analogs can be used to perform 'phase 0' (microdosing) studies at dose levels that have no significant toxic effects
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Molecular imaging provides tools and assays that can address expression of the target protein, drug–target interactions, and tumor response in preclinical and clinical studies
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The number of targets that can be studied noninvasively by molecular imaging is still limited
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Development of new molecular imaging probes for MRI, PET and optical imaging is a highly active research area that will further extend the use of molecular imaging in the process of drug development
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Acknowledgements
We thank the members of the Department of Molecular and Medical Pharmacology, Institute for Molecular Medicine, Crump Institute for Molecular Imaging, and Ahmanson Biological Imaging Division for their helpful conversations.
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Weber, W., Czernin, J., Phelps, M. et al. Technology Insight: novel imaging of molecular targets is an emerging area crucial to the development of targeted drugs. Nat Rev Clin Oncol 5, 44–54 (2008). https://doi.org/10.1038/ncponc0982
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DOI: https://doi.org/10.1038/ncponc0982
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