Rational approach to select small peptide molecular probes labeled with fluorescent cyanine dyes for in vivo optical imaging

Mikhail Y. Berezin, Kevin Guo, Walter Akers, Joseph Livingston, Metasebya Solomon, Hyeran Lee, Kexian Liang, Anthony Agee, Samuel Achilefu

Research output: Contribution to journalArticlepeer-review

71 Scopus citations

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.

Original languageEnglish
Pages (from-to)2691-2700
Number of pages10
JournalBiochemistry
Volume50
Issue number13
DOIs
StatePublished - Apr 5 2011

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