title: Development of a hypoxia-selective near-infrared fluorescent probe for non-invasive tumor imaging.
abstract: A near-infrared fluorochrome, GPU-311, was designed, synthesized and evaluated for its application in non-invasive imaging of tumor hypoxia. Efficient synthesis was achieved by nucleophilic substitution and click chemistry ring using the bifunctional tetraethylene glycol linker 2 containing thiol and azide groups for the conjugation of the propargylated nitroimidazole 1 and the heptamethine cyanine dye 3 bearing a 2-chloro-1-cyclohexenyl ring. GPU-311 exhibited long excitation and emission wavelength (Ex/Em=785/802 nm) and a decent quantum yield (0.05). The water solubility and hydrophilicity of GPU-311 increased. After in vitro treatment of SUIT-2/HRE-Luc pancreatic cancer cells with GPU-311, a higher level of fluorescence was observed selectively in hypoxia than in normoxia. However, in vivo fluorescence imaging of a mouse xenograft model after GPU-311 administration revealed inadequate accumulation of GPU-311 in tumors due to its rapid elimination through the liver.
authors.affiliation: Laboratory of Medicinal and Pharmaceutical Chemistry, Gifu Pharmaceutical University, Gifu, Japan.
authors.forename: Bahaa Gamal Mohamed
authors.initials: BG
authors.lastname: Youssif
authors.forename: Kensuke
authors.initials: K
authors.lastname: Okuda
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Kadonosono
authors.forename: Ola Ibrahim Abdel Razek
authors.initials: OI
authors.lastname: Salem
authors.forename: Alaa Arafat Mohamed
authors.initials: AA
authors.lastname: Hayallah
authors.forename: Mostafa Ahmed
authors.initials: MA
authors.lastname: Hussein
authors.forename: Shinae
authors.initials: S
authors.lastname: Kizaka-Kondoh
authors.forename: Hideko
authors.initials: H
authors.lastname: Nagasawa
mesh_terms: D000818:Animals; D002232:Carbocyanines / Q000737:chemistry; D015687:Cell Hypoxia; D045744:Cell Line, Tumor; D005453:Fluorescence; D005456:Fluorescent Dyes / Q000138:chemical synthesis* / Q000737:chemistry; D006801:Humans; D057927:Hydrophobic and Hydrophilic Interactions; D051379:Mice; D009369:Neoplasms / Q000175:diagnosis* / Q000378:metabolism / Q000473:pathology; D009593:Nitroimidazoles / Q000737:chemistry; D012995:Solubility; D019265:Spectroscopy, Near-Infrared / Q000379:methods
chemical_list: D002232:Carbocyanines; D005456:Fluorescent Dyes; D009593:Nitroimidazoles; C089187:cyanine dye 3