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Nature Medicine 8, 757 - 761 (2002)
Published online: 24 June 2002 | doi:10.1038/nm729
Fluorescence molecular tomography resolves protease activity in vivo
Vasilis Ntziachristos1, Ching-Hsuan Tung1, Christoph Bremer1 & Ralph Weissleder1
- Center for Molecular Imaging Research, Massachusetts General Hospital and Harvard Medical School, Charlestown, Massachusetts, USA
Correspondence to: Vasilis Ntziachristos1 e-mail: vasilis@helix.mgh.harvard.edu
Abstract
Systematic efforts are under way to develop novel technologies that would allow molecular sensing in intact organisms in vivo. Using near-infrared fluorescent molecular beacons and inversion techniques that take into account the diffuse nature of photon propagation in tissue, we were able to obtain three-dimensional in vivo images of a protease in orthopic gliomas. We demonstrate that enzyme-activatable fluorochromes can be detected with high positional accuracy in deep tissues, that molecular specificities of different beacons towards enzymes can be resolved and that tomography of beacon activation is linearly related to enzyme concentration. The tomographic imaging method offers a range of new capabilities for studying biological function; for example, identifying molecular-expression patterns by multispectral imaging or continuously monitoring the efficacy of therapeutic drugs.
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