Whole-animal cellular and molecular imaging to accelerate drug development

doi:10.1016/S1359-6446(02)02268-7

Drug Discovery Today

Volume 7, Issue 10, 15 May 2002, Pages 555-562

https://doi.org/10.1016/S1359-6446(02)02268-7 Get rights and content

Abstract

In the past decade, new technologies (genomics), chemistries and high-throughput (HT) in vitro assays have played a large role in changing the paradigm of drug discovery and development. These technologies have enabled many more targets and potential lead compounds to be introduced into drug development. However, since 1996, the number of drug approvals per year has been decreasing. This reduced pipeline has now compromised the ability of biopharmaceutical companies to deliver the double-digit growth levels that investors expect. This review explores what is lacking in the drug discovery and development process that has caused such a dearth of new chemical entities (NCEs), and looks at how new in vivo imaging technologies might provide an answer in the form of more predictive animal models.

Section snippets

Transgenic animals

Mice or rats that contain a modified endogenous gene or a reporter gene integrated into the genome of their germ cells are called transgenic animals. These animals can be bred and the gene of interest passed to the offspring as a mendelian trait. Our knowledge of the mouse and human genomes allows transgenic animals to be made that contain a corresponding mutation for many human genetic diseases for which a specific gene has been identified and characterized. Transgenic animals are used to

Whole-animal cell and molecular imaging methods

By imaging the whole animal at multiple time points, researchers can better understand disease pathology, pharmacokinetics and other contextual aspects of the biomolecular processes taking place in the living animal. This reduces the statistical variability that is inherent in traditional ex vivo methodologies in which data are compared among different groups of animals that must be sacrificed during the course of the protocol to obtain the data. In whole-animal imaging technologies, each

Summary

Transgenic technology will continue to build on advances in the successful sequencing of the human and mouse genomes and on progress in the area of proteomics [42]. These advances have made it practical for the first time to undertake many lines of genetic research that will inevitably point the way to many more potential drug targets and, ultimately, the development of new NCEs. The advances in whole-animal cellular and molecular imaging now enable a more comprehensive analysis of gene

Acknowledgements

I would like to thank John Thomas for research, editing and manuscript preparation, Robin Kurka for manuscript preparation and Christopher Contag for comments and editing regarding the field of whole-animal imaging.

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ReviewWhole-animal cellular and molecular imaging to accelerate drug development

Abstract

Section snippets

Transgenic animals

Whole-animal cell and molecular imaging methods

Summary

Acknowledgements

J. Biol. Chem.

Cell

Trends Biotechnol.

Semin. Nucl. Med.

J. Nucl. Cardiol.

Acad. Radiol.

Acad. Radio.

Mol. Ther.

Neoplasia