title: Photoacoustic lifetime contrast between methylene blue monomers and self-quenched dimers as a model for dual-labeled activatable probes.
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.
authors: University of Minnesota, Department of Biomedical Engineering, Minneapolis, MN 55455, USA. emorgoun@umn.edu
authors: Ekaterina
authors: E
authors: Morgounova
authors: Qi
authors: Q
authors: Shao
authors: Benjamin J
authors: BJ
authors: Hackel
authors: David D
authors: DD
authors: Thomas
authors: Shai
authors: S
authors: Ashkenazi
mesh_terms: D003952:Diagnostic Imaging / Q000379:methods; D019281:Dimerization; D005456:Fluorescent Dyes / Q000737:chemistry*; D008751:Methylene Blue / Q000737:chemistry*; D008956:Models, Chemical; D061088:Photoacoustic Techniques / Q000379:methods*; D012967:Sodium Dodecyl Sulfate / Q000737:chemistry; D013431:Sulfates / Q000737:chemistry
chemical_list: D005456:Fluorescent Dyes; D013431:Sulfates; C012036:sodium sulfate; D012967:Sodium Dodecyl Sulfate; D008751:Methylene Blue
references: Biopolymers. 2004;76(5):391-403
references: 15389488
references: Annu Rev Biochem. 1985;54:43-71
references: 3896124
references: J Photochem Photobiol B. 2000 Sep;57(2-3):186-92
references: 11154085
references: Clin Cancer Res. 2013 Mar 15;19(6):1494-502
references: 23349314
references: Curr Org Synth. 2011 Aug;8(4):498-520
references: 23519774
references: Chemphyschem. 2009 Jul 13;10(9-10):1389-98
references: 19475638
references: J Biochem Biophys Methods. 1983 May;7(3):243-54
references: 6875183
references: Photochem Photobiol. 2003 May;77(5):459-68
references: 12812286
references: Exp Dermatol. 2009 Jun;18(6):509-15
references: 19243426
references: Proc Natl Acad Sci U S A. 2004 Dec 21;101(51):17867-72
references: 15601762
references: Cancer Res. 2012 Jun 1;72(11):2738-45
references: 22491533
references: Radiat Res. 1963 Sep;20:55-70
references: 14061481
references: Amino Acids. 2011 Nov;41(5):1113-22
references: 20953646
references: Opt Express. 2012 May 21;20(11):11582-97
references: 22714144
references: Nat Biotechnol. 1996 Mar;14(3):303-8
references: 9630890
references: Eur J Clin Pharmacol. 2000 Jun;56(3):247-50
references: 10952480
references: Biotechniques. 2001 Nov;31(5):1106-16, 1118, 1120-1
references: 11730017
references: Am J Ther. 2003 Jul-Aug;10(4):289-91
references: 12845393
references: Nat Med. 2002 Jul;8(7):757-60
references: 12091907
references: J Am Chem Soc. 2010 Aug 18;132(32):11264-9
references: 20698693
references: Biochem Biophys Res Commun. 2011 Jan 14;404(2):581-6
references: 21130738
references: J Pharm Sci. 1986 Apr;75(4):384-6
references: 3723360
references: J Pharm Sci. 1972 Jul;61(7):1086-90
references: 5044807
references: Cold Spring Harb Protoc. 2011 Sep 01;2011(9):
references: 21880823
references: Biochemistry. 1990 Jun 5;29(22):5270-5
references: 2383545
references: Proc Natl Acad Sci U S A. 2001 Dec 18;98(26):14997-5002
references: 11752448
references: Photochem Photobiol. 1999 Oct;70(4):391-475
references: 10546544
references: J Biomed Opt. 2010 Jul-Aug;15(4):040501
references: 20799768
references: J Biomed Opt. 2012 Jan;17(1):011002
references: 22352636
references: Langmuir. 2009 Sep 15;25(18):10490-4
references: 19735127
references: Talanta. 2010 May 15;81(3):760-5
references: 20298850
references: Opt Express. 2008 Nov 10;16(23):18605-15
references: 19581946
references: J Biomed Opt. 2010 Mar-Apr;15(2):021315
references: 20459237
references: Nat Biotechnol. 1999 Apr;17(4):375-8
references: 10207887