In vitro characterization of a lifetime-based activatable photoacoustic probe

Ekaterina Morgounova; Sadie M. Johnson; Qi Shao; Benjamin J. Hackel; Michael Wilson; Shai Ashkenazi

doi:10.1117/12.2080362

13 March 2015 In vitro characterization of a lifetime-based activatable photoacoustic probe

Ekaterina Morgounova, Sadie M. Johnson, Qi Shao, Benjamin J. Hackel, Michael Wilson, Shai Ashkenazi

Proceedings Volume 9323, Photons Plus Ultrasound: Imaging and Sensing 2015; 93232J (2015) https://doi.org/10.1117/12.2080362
Event: SPIE BiOS, 2015, San Francisco, California, United States

Abstract

Activatable photoacoustic probes hold great promise for in vivo imaging of enzyme activity as they exhibit high contrast and high selectivity at depths similar to that of ultrasound imaging. Here we report the synthesis and testing of a matrix metalloproteinase 2 (MMP-2) specific peptide probe capable of changing its transient photoacoustic lifetime from short to long after activation. The intact probe comprises an enzyme-specific cleavable sequence conjugated to a pair of methylene blue (MB) molecules that dimerize due to forced proximity, resulting in static quenching. Upon cleavage, the MB molecules dissociate and recover their intrinsic excited-state lifetime of more than 2 μs. We demonstrated using a pump-probe photoacoustic imaging approach that the cleaved probe exhibits a transient signal with lifetime comparable to that of MB monomers, whereas no lifetime was detected for the intact probe. This could allow for detection of the cleaved probe in the presence of high levels of intact probe as well as short transients due to endogenous tissue absorbers, thereby providing high contrast and low background noise. Finally, we have compared peptide sequences of varying length and structure using absorption spectrometry in order to select the probe best suited for our imaging needs. Our results suggest that both factors could potentially have an impact on dimerization efficiency and the cleavage rate of the peptide. However, all probes provided a high degree of dimerization and efficient separation after cleavage, indicating that a lifetime-based activatable peptide can be constructed for in vivo applications using a two-wavelength imaging approach.

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Ekaterina Morgounova, Sadie M. Johnson, Qi Shao, Benjamin J. Hackel, Michael Wilson, and Shai Ashkenazi "In vitro characterization of a lifetime-based activatable photoacoustic probe", Proc. SPIE 9323, Photons Plus Ultrasound: Imaging and Sensing 2015, 93232J (13 March 2015); https://doi.org/10.1117/12.2080362

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KEYWORDS

Photoacoustic spectroscopy

Molecules

Absorption

Ultrasonography

Photoacoustic imaging

In vivo imaging

Signal detection

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