Nature Biotechnology 24, 339 - 343 (2006)
Published online: 26 February 2006; | doi:10.1038/nbt1188
Self-illuminating quantum dot conjugates for in vivo imagingMin-Kyung So1, 4, Chenjie Xu1, 4, Andreas M Loening1, 2, Sanjiv S Gambhir1, 2
& Jianghong Rao1, 31
Molecular Imaging Program at Stanford, Department of Radiology & Bio-X Program, Stanford University, 1201 Welch Road, Stanford, California 94305-5484, USA. 2
Department of Bioengineering, Stanford University, 1201 Welch Road, Stanford, California 94305-5484, USA. 3
Biophysics Program, Stanford University, 1201 Welch Road, Stanford, California 94305-5484, USA. 4
These authors contributed equally to this work.
Correspondence should be addressed to Jianghong Rao jrao@stanford.edu Fluorescent semiconductor quantum dots hold great potential for molecular imaging in vivo
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5. However, the utility of existing quantum dots for in vivo imaging is limited because they require excitation from external illumination sources to fluoresce, which results in a strong autofluorescence background and a paucity of excitation light at nonsuperficial locations. Here we present quantum dot conjugates that luminesce by bioluminescence resonance energy transfer in the absence of external excitation. The conjugates are prepared by coupling carboxylate-presenting quantum dots to a mutant of the bioluminescent protein Renilla reniformis luciferase. We show that the conjugates emit long-wavelength (from red to near-infrared) bioluminescent light in cells and in animals, even in deep tissues, and are suitable for multiplexed in vivo imaging. Compared with existing quantum dots, self-illuminating quantum dot conjugates have greatly enhanced sensitivity in small animal imaging, with an in vivo signal-to-background ratio of > 103 for 5 pmol of conjugate.
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