Imaging Drug Responses

The ability to non-invasively image molecular processes in-vivo is an emerging reality using different reporter and detection approaches. Molecular imaging has been heralded to lead to earlier detection than current anatomical imaging approaches, which typically detect late stage abnormalities. Another important prospect of molecular imaging is the ability to examine and quantify treatment responses in-vivo by monitoring specific primary molecules or downstream targets. Therapeutic efficacy could then be probed dynamically on time-scales of hours to days. This is in contrast to the mainstay of today's healthcare with traditionally late end points of drug efficacy, a practice that often impairs prompt revision and exclusion of ineffective treatment strategies with potentially lethal results.

Tomographic techniques based on accurate modeling of photon propagation in tissues and subsequent mathematical inversion have the possibility to overcome the limitations of planar imaging, and provide quantitative three-dimensional information of optical contrast. Figure 1 shows images of apoptotic tumor response following treatment obtained in-vivo from an animal implanted with a sensitive (left side) and resistant (right side) Lewis Lung Carcinoma tumors.

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Figure 1.
Imaging apoptotic response in-vivo: (a) Planar fluorescence image (b) Four consecutive FMT slices (in color) superimposed on the planar image of the mouse obtained at the excitation wavelength. The bottom right slice is the one closer to the surface of the animal as seen on (a) and successive slices are reconstructed from deeper in the animal. (c,d) TUNEL stained histological slices from the sensitive and resistant tumors.

This technology has further shown superior quantification performance in relation to planar imaging methods, even for superficial tumors.

For details see Ntziachristos V. et. al. Proc. Natl. Acad. Sci. USA 101: 12294-12299, 2004