Deep-tissue imaging of intramolecular fluorescence resonance energy-transfer parameters.

We demonstrate the in vivo reconstruction of all fluorescence resonance energy transfer (FRET) parameters, including the nanometer donor-acceptor distance, in a mouse. The FRET chemical targets cancer cells, and on internalization, the acceptor is released, in lieu of a targeted anticancer drug in chemotherapy. Our method provides a new vehicle for studying disease by imaging FRET parameters in deep tissue.

[1]  M. Ikura,et al.  The use of FRET imaging microscopy to detect protein-protein interactions and protein conformational changes in vivo. , 2001, Current opinion in structural biology.

[2]  Ammasi Periasamy,et al.  Illuminating protein interactions in tissue using confocal and two-photon excitation fluorescent resonance energy transfer microscopy. , 2003, Journal of biomedical optics.

[3]  Alessandro Sardini,et al.  Three-dimensional imaging of Förster resonance energy transfer in heterogeneous turbid media by tomographic fluorescent lifetime imaging. , 2009, Optics letters.

[4]  Kevin J Webb,et al.  Three-dimensional Bayesian optical diffusion tomography with experimental data. , 2002, Optics letters.

[5]  Isabelle Richard,et al.  Imaging calpain protease activity by multiphoton FRET in living mice. , 2005, Journal of molecular biology.

[6]  Vaibhav Gaind,et al.  Towards in vivo imaging of intramolecular fluorescence resonance energy transfer parameters. , 2009, Journal of the Optical Society of America. A, Optics, image science, and vision.

[7]  Th. Förster Zwischenmolekulare Energiewanderung und Fluoreszenz , 1948 .

[8]  Philip S Low,et al.  Discovery and development of folic-acid-based receptor targeting for imaging and therapy of cancer and inflammatory diseases. , 2008, Accounts of chemical research.

[9]  G. M. Hale,et al.  Optical Constants of Water in the 200-nm to 200-microm Wavelength Region. , 1973, Applied optics.

[10]  Philip S Low,et al.  Evaluation of disulfide reduction during receptor-mediated endocytosis by using FRET imaging , 2006, Proceedings of the National Academy of Sciences.

[11]  Elisha Haas,et al.  The study of protein folding and dynamics by determination of intramolecular distance distributions and their fluctuations using ensemble and single-molecule FRET measurements. , 2005, Chemphyschem : a European journal of chemical physics and physical chemistry.