Design, synthesis, and imaging of an activatable photoacoustic probe

Jelena Levi, Sri-Rajasekhar Kothapalli, Te Jen Ma, Keith Hartman, Butrus T. Khuri-Yakub, Sanjiv Sam Gambhir

Research output: Contribution to journalArticle

122 Citations (Scopus)

Abstract

Photoacoustic tomography is a rapidly growing imaging modality that can provide images of high spatial resolution and high contrast at depths up to 5 cm. We report here the design, synthesis, and evaluation of an activatable probe that shows great promise for enabling detection of the cleaved probe in the presence of high levels of nonactivated, uncleaved probe, a difficult task to attain in absorbance-based modality. Before the cleavage by its target, proteolytic enzyme MMP-2, the probe, an activatable cell-penetrating peptide, Ceeee[Ahx]PLGLAGrrrrrK, labeled with two chromophores, BHQ3 and Alexa750, shows photoacoustic signals of similar intensity at the two wavelengths corresponding to the absorption maxima of the chromophores, 675 and 750 nm. Subtraction of the images taken at these two wavelengths makes the probe effectively photoacoustically silent, as the signals at these two wavelengths essentially cancel out. After the cleavage, the dye associated with the cell-penetrating part of the probe, BHQ3, accumulates in the cells, while the other dye diffuses away, resulting in photoacoustic signal seen at only one of the wavelengths, 675 nm. Subtraction of the photoacoustic images at two wavelengths reveals the location of the cleaved (activated) probe. In the search for the chromophores that are best suited for photoacoustic imaging, we have investigated the photoacoustic signals of five chromophores absorbing in the near-infrared region. We have found that the photoacoustic signal did not correlate with the absorbance and fluorescence of the molecules, as the highest photoacoustic signal arose from the least absorbing quenchers, BHQ3 and QXL 680.

Original languageEnglish (US)
Pages (from-to)11264-11269
Number of pages6
JournalJournal of the American Chemical Society
Volume132
Issue number32
DOIs
StatePublished - Aug 18 2010

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Photoacoustic effect
Coloring Agents
Cell-Penetrating Peptides
Imaging techniques
Chromophores
Matrix Metalloproteinases
Peptide Hydrolases
Wavelength
Fluorescence
Tomography
Dyes
Peptides
Infrared radiation
Molecules

All Science Journal Classification (ASJC) codes

  • Catalysis
  • Chemistry(all)
  • Biochemistry
  • Colloid and Surface Chemistry

Cite this

Levi, Jelena ; Kothapalli, Sri-Rajasekhar ; Ma, Te Jen ; Hartman, Keith ; Khuri-Yakub, Butrus T. ; Gambhir, Sanjiv Sam. / Design, synthesis, and imaging of an activatable photoacoustic probe. In: Journal of the American Chemical Society. 2010 ; Vol. 132, No. 32. pp. 11264-11269.
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Levi, J, Kothapalli, S-R, Ma, TJ, Hartman, K, Khuri-Yakub, BT & Gambhir, SS 2010, 'Design, synthesis, and imaging of an activatable photoacoustic probe', Journal of the American Chemical Society, vol. 132, no. 32, pp. 11264-11269. https://doi.org/10.1021/ja104000a

Design, synthesis, and imaging of an activatable photoacoustic probe. / Levi, Jelena; Kothapalli, Sri-Rajasekhar; Ma, Te Jen; Hartman, Keith; Khuri-Yakub, Butrus T.; Gambhir, Sanjiv Sam.

In: Journal of the American Chemical Society, Vol. 132, No. 32, 18.08.2010, p. 11264-11269.

Research output: Contribution to journalArticle

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