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Fluorescence molecular tomography resolves protease activity in vivo

Nature Medicine volume 8, pages 757–761 (2002)Cite this article

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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Figure 1: Schematic of the FMT imager used for the experimental measurements.
Figure 2: In vitro evaluation of tomographic capacity.
Figure 3: In vivo FMT of cathepsin B expression levels in 9L gliosarcomas stereotactically implanted into unilateral brain hemispheres of nude mice.

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Authors and Affiliations

  1. Center for Molecular Imaging Research, Massachusetts General Hospital and Harvard Medical School, Charlestown, Massachusetts, USA

    Vasilis Ntziachristos, Ching-Hsuan Tung, Christoph Bremer & Ralph Weissleder

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  1. Vasilis Ntziachristos
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  2. Ching-Hsuan Tung
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  3. Christoph Bremer
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  4. Ralph Weissleder
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Correspondence to Vasilis Ntziachristos.

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Ntziachristos, V., Tung, CH., Bremer, C. et al. Fluorescence molecular tomography resolves protease activity in vivo. Nat Med 8, 757–761 (2002). https://doi.org/10.1038/nm729

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