Research Papers: Imaging

Photoacoustic lifetime contrast between methylene blue monomers and self-quenched dimers as a model for dual-labeled activatable probes

[+] Author Affiliations
Ekaterina Morgounova, Qi Shao, Shai Ashkenazi

University of Minnesota, Department of Biomedical Engineering, 312 Church Street SE, Minneapolis, Minnesota 55455

Benjamin J. Hackel

University of Minnesota, Department of Chemical Engineering and Materials Science, 421 Washington Ave. SE, Minneapolis, Minnesota 55455

David D. Thomas

University of Minnesota, Department of Biochemistry, Molecular Biology and Biophysics, 321 Church Street SE, Minneapolis, Minnesota 55455

J. Biomed. Opt. 18(5), 056004 (May 02, 2013). doi:10.1117/1.JBO.18.5.056004
History: Received December 2, 2012; Revised March 19, 2013; Accepted March 26, 2013
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Abstract.  Activatable photoacoustic probes efficiently combine the high spatial resolution and penetration depth of ultrasound with the high optical contrast and versatility of molecular imaging agents. Our approach is based on photoacoustic probing of the excited-state lifetime of methylene blue (MB), a fluorophore widely used in clinical therapeutic and diagnostic applications. Upon aggregation, static quenching between the bound molecules dramatically shortens their lifetime by three orders of magnitude. We present preliminary results demonstrating the ability of photoacoustic imaging to probe the lifetime contrast between monomers and dimers with high sensitivity in cylindrical phantoms. Gradual dimerization enhancement, driven by the addition of increasing concentrations of sodium sulfate to a MB solution, showed that lifetime-based photoacoustic probing decreases linearly with monomer concentration. Similarly, the addition of 4 mM sodium dodecyl sulfate, a concentration that amplifies MB aggregation and reduces the monomer concentration by more than 20-fold, led to a signal decrease of more than 20 dB compared to a solution free of surfactant. These results suggest that photoacoustic imaging can be used to selectively detect the presence of monomers. We conclude by discussing the implementation of the monomer–dimer contrast mechanism for the development of an enzyme-specific activatable probe.

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© 2013 Society of Photo-Optical Instrumentation Engineers

Citation

Ekaterina Morgounova ; Qi Shao ; Benjamin J. Hackel ; David D. Thomas and Shai Ashkenazi
"Photoacoustic lifetime contrast between methylene blue monomers and self-quenched dimers as a model for dual-labeled activatable probes", J. Biomed. Opt. 18(5), 056004 (May 02, 2013). ; http://dx.doi.org/10.1117/1.JBO.18.5.056004


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