title: Glucosamine-linked near-infrared fluorescent probes for imaging of solid tumor xenografts.
abstract: OBJECTIVE
  Near-infrared fluorescence (NIRF) imaging is an attractive technique for studying diseases at the molecular level in vivo. Glucose transporters are often used as targets for in vivo imaging of tumors. The efficiency of a tumor-seeking fluorescent probe can be enhanced by attaching one or more glucosamine (GlcN) moieties. This study was designed to evaluate the use of previously developed GlcN-linked NIRF probes for in vitro and in vivo optical imaging of cancer.
  
  
  METHODS
  Cellular uptake of the probes (1 μM) was investigated in monolayer cultures of luciferase-expressing PC3 (PC3-luc) cells. The prostate tumors were established as subcutaneous xenografts using PC3-luc cells in nude mice. The biodistributions and tumor-targeting specificities of cypate (cyp), cypate-D: -(+)-glucosamine (cyp-GlcN), and D: -(+)-gluosamine-cypate-D: -(+)-gluosamine (cyp-2GlcN) were studied. The tumor, muscle, and major organs were collected for ex vivo optical imaging.
  
  
  RESULTS
  The tumor cell uptake of the probe containing two glucosamine residues, cyp-2GlcN, was significantly higher than the uptake of both the probe with one glucosamine residue, cyp-GlcN, and the probe without glucosamine, cyp only. Similarly, in in vivo experiments, cyp-2GlcN demonstrated higher maximum fluorescence intensity and longer residence lifetime in tumors than cyp-GlcN or cyp. The ex vivo biodistribution analysis revealed that tumor uptake of cyp-2GlcN and cyp-GlcN was four- and twofold higher than that of cyp at 24 h post-injection, respectively.
  
  
  CONCLUSIONS
  Both cyp-GlcN and cyp-2GlcN NIRF probes exhibited good tumor-targeting properties in prostate cancer cell cultures and live mice. The cyp-2GlcN probe showed the highest uptake with good retention characteristics in vivo. The uptake of cyp-2GlcN and cyp-GlcN is likely mediated by glucosamine-recognizing transporters. The uptake mechanism is being explored further for developing cypate-glucosamine-based probes for in vivo imaging.
authors.affiliation: Molecular Imaging Laboratory, Department of Radiology, Howard University, Washington, DC, USA.
authors.forename: Alexandru V
authors.initials: AV
authors.lastname: Korotcov
authors.forename: Yunpeng
authors.initials: Y
authors.lastname: Ye
authors.forename: Yue
authors.initials: Y
authors.lastname: Chen
authors.forename: Fayun
authors.initials: F
authors.lastname: Zhang
authors.forename: Sophia
authors.initials: S
authors.lastname: Huang
authors.forename: Stephen
authors.initials: S
authors.lastname: Lin
authors.forename: Rajagopalan
authors.initials: R
authors.lastname: Sridhar
authors.forename: Samuel
authors.initials: S
authors.lastname: Achilefu
authors.forename: Paul C
authors.initials: PC
authors.lastname: Wang
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D004705:Endocytosis; D005456:Fluorescent Dyes / Q000737:chemistry; D005944:Glucosamine / Q000737:chemistry; D006801:Humans; D007700:Kinetics; D008297:Male; D051379:Mice; D008819:Mice, Nude; D057054:Molecular Imaging / Q000379:methods*; D009369:Neoplasms / Q000175:diagnosis* / Q000473:pathology; D055096:Optical Devices; D011471:Prostatic Neoplasms / Q000175:diagnosis / Q000473:pathology; D019265:Spectroscopy, Near-Infrared; D014018:Tissue Distribution; D023041:Xenograft Model Antitumor Assays
chemical_list: D005456:Fluorescent Dyes; D005944:Glucosamine