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

Abstract

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.

Switchable Photoacoustic Intensity of Methylene Blue via Sodium Dodecyl Sulfate Micellization

“…In addition to spectral data, Carroll et al detected increased scattering signal 22 , and Morgounova et al detected decreased triplet transient absorption at 660 nm 18 of MB in SDS at premicellar concentrations. This suggested the presence of MB/SDS clusters.…”

“…For example, Morgounova et al measured the difference in PA lifetime contrast between MB monomers and dimers, suggesting potentials for an activatable probe using enzymatic cleavage. 18 PA monitoring of MB can also measure changes in the local tissue environment. Ashkenazi used MB to measure dissolved oxygen in biological tissues because the PA lifetime of MB decreased due to energy transfer to oxygen.…”

Manifestation of intermolecular interactions in FTIR spectra of methylene blue molecules

“…Among them there are chemical indicators, markers, and spectral sensitization systems, biocompatible agents for photodynamic therapy [1][2][3][4][5].…”

Methylene Blue and Hydrogen Peroxide for Photodynamic Inactivation in Root Canal - A New Protocol for Use in Endodontics

“…Static quenching involves aggregation of the MB molecules. MB can form self-quenched dimers that according to Morgounova et al (25) can reduce the excited state lifetime of MB by three orders of magnitude. A report by McCullagh and Robertson (16) found that at higher concentrations, MB formed dimeric compounds also reducing the efficiency of the system.…”