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Special Section on Photons Plus Ultrasound: Imaging and Sensing

In vitro testing of a protease-sensitive contrast agent for optoacoustic imaging

[+] Author Affiliations
Anthony H. Green, James R. Norris

The University of Chicago, Department of Chemistry, 5735 S. Ellis Avenue, Chicago, Illinois 60637

Jing Wang, Zhixing Xie, Hao F. Zhang

University of Wisconsin-Milwaukee, Department of Electrical Engineering and Computer Science, 2200 E. Kenwood Boulevard, Milwaukee, Wisconsin 53201-0413

Patrick J. La Riviere

The University of Chicago, Department of Radiology, 5841 S. Maryland Avenue, Chicago, Illinois 60637

J. Biomed. Opt. 15(2), 021315 (August 18, 2009December 23, 2009December 28, 2009March 29, 2010March 29, 2010). doi:10.1117/1.3365935
History: Received August 18, 2009; Revised December 23, 2009; Accepted December 28, 2009; Published March 29, 2010; Online March 29, 2010
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We have designed a protease-sensitive imaging probe for optoacoustic imaging whose absorption spectrum changes upon cleavage by a protease of interest. The probe comprises an active site, a derivative of chlorophyll or natural photosynthetic bacteriochlorophyll that absorbs in the near infrared, conjugated to a peptide backbone specific to the protease being imaged. The uncleaved molecules tend to aggregate in dimers and trimers, causing a change in the absorption spectrum relative to that of the monomer. Upon cleavage, the probe molecules deaggregate, giving rise to a spectrum characteristic of monomers. We show using photospectrometry that the two forms of the probe have markedly different absorption spectra, which could allow for in vivo optoacoustic identification using a multiwavelength imaging strategy. Optoacoustic measurements using a narrow-band dye laser find spectral peaks in the two forms of the probe at the expected location. The optoacoustic signal from the uncleaved probe is found to be considerably weaker than that of the cleaved probe, perhaps due to poor optical-acoustic coupling in the aggregated molecules. However, ultimately, it is detection of the cleaved probe that is of the greatest import, since it reports on the protease activity of interest.

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© 2010 Society of Photo-Optical Instrumentation Engineers

Citation

Anthony H. Green ; Jing Wang ; Patrick J. La Riviere ; Zhixing Xie ; James R. Norris, et al.
"In vitro testing of a protease-sensitive contrast agent for optoacoustic imaging", J. Biomed. Opt. 15(2), 021315 (August 18, 2009December 23, 2009December 28, 2009March 29, 2010March 29, 2010). ; http://dx.doi.org/10.1117/1.3365935


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