title: Rational approach to select small peptide molecular probes labeled with fluorescent cyanine dyes for in vivo optical imaging.
abstract: We demonstrate that the structure of carbocyanine dyes, which are commonly used to label small peptides for molecular imaging and not the bound peptide, controls the rate of extravasation from blood vessels to tissue. By examining several near-infrared (NIR) carbocyanine fluorophores, we demonstrate a quantitative correlation between the binding of a dye to albumin, a model plasma protein, and the rate of extravasation of the probe into tissue. Binding of the dyes was measured by fluorescence quenching of the tryptophans in albumin and was found to be inversely proportional to the rate of extravasation. The rate of extravasation, determined by kurtosis from longitudinal imaging studies using rodent ear models, provided a basis for quantitative measurements. Structure-activity studies aimed at evaluating a representative library of NIR fluorescent cyanine probes showed that hydrophilic dyes with binding constants several orders of magnitude lower than their hydrophobic counterparts have much faster extravasation rate, establishing a foundation for rational probe design. The correlation provides a guideline for dye selection in optical imaging and a method to verify if a certain dye is optimal for a specific molecular imaging application.
authors.affiliation: Department of Radiology, Washington University, St. Louis, Missouri 63110, United States.
authors.forename: Mikhail Y
authors.initials: MY
authors.lastname: Berezin
authors.forename: Kevin
authors.initials: K
authors.lastname: Guo
authors.forename: Walter
authors.initials: W
authors.lastname: Akers
authors.forename: Joseph
authors.initials: J
authors.lastname: Livingston
authors.forename: Metasebya
authors.initials: M
authors.lastname: Solomon
authors.forename: Hyeran
authors.initials: H
authors.lastname: Lee
authors.forename: Kexian
authors.initials: K
authors.lastname: Liang
authors.forename: Anthony
authors.initials: A
authors.lastname: Agee
authors.forename: Samuel
authors.initials: S
authors.lastname: Achilefu
mesh_terms: D000818:Animals; D002232:Carbocyanines / Q000737:chemistry / Q000378:metabolism* / Q000493:pharmacokinetics; D005119:Extravasation of Diagnostic and Therapeutic Materials; D005456:Fluorescent Dyes / Q000737:chemistry / Q000378:metabolism* / Q000493:pharmacokinetics; D057927:Hydrophobic and Hydrophilic Interactions; D007700:Kinetics; D051379:Mice; D057054:Molecular Imaging / Q000379:methods*; D015335:Molecular Probes / Q000737:chemistry / Q000378:metabolism* / Q000493:pharmacokinetics; D009842:Oligopeptides / Q000737:chemistry / Q000378:metabolism* / Q000493:pharmacokinetics; D012710:Serum Albumin, Bovine / Q000378:metabolism; D013329:Structure-Activity Relationship
chemical_list: D002232:Carbocyanines; D005456:Fluorescent Dyes; D015335:Molecular Probes; D009842:Oligopeptides; D012710:Serum Albumin, Bovine