title: Near-infrared indocyanine dye permits real-time characterization of both venous and lymphatic circulation.
abstract: We investigated the optical properties of a near-infrared (NIR) fluorochrome, di-β-cyclodextrin-binding indocyanine derivative (TK-1), and its pharmacokinetic differences with indocyanine green (ICG). TK-1 was designed to have hydrophilic cyclodextrin molecules and, thus, for higher water solubility and smaller particle sizes than the plasma protein-bound ICG. We compared optical properties such as the absorption and fluorescence spectra, quantum yield, and photostability between both dyes in vitro. In addition, we subcutaneously injected a 1 mM solution of TK-1 or ICG into the hind footpad of rats and observed real-time NIR fluorescence intensities in their femoral veins and accompanying lymphatics at the exposed groin site to analyze the dye pharmacokinetics. These optical experiments demonstrated that TK-1 has high water solubility, a low self-aggregation tendency, and high optical and chemical stabilities. Our in vivo imaging showed that TK-1 was transported via peripheral venous flow and lymphatic flow, whereas ICG was drained only through lymphatics. The results of this study showed that lymphatic and venous transport can be differentially regulated and is most likely influenced primarily by particle size, and that TK-1 can enable real-time NIR fluorescence imaging of whole fluids and solute movement via both microvessels and lymphatics, which conventional ICG cannot achieve.
authors.affiliation: Nagoya University, Department of Hand Surgery, 65 Tsurumai-cho, Showa-ku, Nagoya 466-8550, JapanbAnjo Kosei Hospital, Hand and Microsurgery Center, 28 Higashihirokute, Anjo-cho, Anjo 446-8602, Japan.
authors.forename: Toshikazu
authors.initials: T
authors.lastname: Kurahashi
authors.affiliation: Nagoya University, Department of Hand Surgery, 65 Tsurumai-cho, Showa-ku, Nagoya 466-8550, Japan.
authors.forename: Katsuyuki
authors.initials: K
authors.lastname: Iwatsuki
authors.affiliation: Nagoya University, Department of Hand Surgery, 65 Tsurumai-cho, Showa-ku, Nagoya 466-8550, Japan.
authors.forename: Tetsuro
authors.initials: T
authors.lastname: Onishi
authors.affiliation: Gifu Prefectural Tajimi Hospital, Department of Orthopedic Surgery, 5-161 Maehata-cho, Tajimi 507-8522, Japan.
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Arai
authors.affiliation: Mie University, Department of Life Sciences, Regulatory Biochemistry, 1577 Kurimamachiya-cho, Tsu 514-8507, Japan.
authors.forename: Katsunori
authors.initials: K
authors.lastname: Teranishi
authors.affiliation: Nagoya University, Department of Hand Surgery, 65 Tsurumai-cho, Showa-ku, Nagoya 466-8550, Japan.
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Hirata
mesh_terms: D000818:Animals; D005453:Fluorescence; D007208:Indocyanine Green / Q000378:metabolism*; D007259:Infrared Rays; D042601:Lymphatic Vessels / Q000000981:diagnostic imaging*; D051381:Rats; D014680:Veins / Q000000981:diagnostic imaging*
chemical_list: D007208:Indocyanine Green