title: Optical glucose analogs of aminolevulinic acid for fluorescence-guided tumor resection and photodynamic therapy.
abstract: OBJECTIVE
  We have developed and tested a novel conjugation of the clinically used prodrug aminolevulinic acid with 2-deoxyglucosamine as a novel probe (ALA-2DG) for fluorescence imaging and photodynamic therapy.
  
  
  METHODS
  ALA-2DG was successfully synthesized, and the mechanisms of probe uptake, PpIX synthesis, and photodynamic therapy efficacy were evaluated in vitro and in vivo.
  
  
  RESULTS
  ALA-2DG led to PpIX synthesis in tumor cells in vitro and in tumor in vivo. Competitive and inhibitory assays in vitro showed a reduction of this PpIX synthesis that was not observed when cells were incubated with ALA itself, indicating that intracellular uptake of ALA-2DG occurs by GLUT-mediated active transport. Initial photodynamic therapy studies confirmed the efficacy of ALA-2DG as a photodynamic sensitizer.
  
  
  CONCLUSIONS
  The in vitro assays suggest that ALA-2DG is taken up by cells via glucose transporters. Initial studies in oral cancer demonstrated the applicability of ALA-2DG for in vivo imaging and its potential as an alternative to ALA-PpIX-based fluorescence diagnostics and photodynamic therapy, providing higher tumor specificity.
authors: Ontario Cancer Institute, University Heath Network, Toronto, Ontario, Canada, edmoriyama@gmail.com.
authors: Eduardo H
authors: EH
authors: Moriyama
authors: Weiguo
authors: W
authors: Cao
authors: Tracy W
authors: TW
authors: Liu
authors: Han Lin
authors: HL
authors: Wang
authors: Peter D
authors: PD
authors: Kim
authors: Juan
authors: J
authors: Chen
authors: Gang
authors: G
authors: Zheng
authors: Brian C
authors: BC
authors: Wilson
mesh_terms: D009327:4-Chloro-7-nitrobenzofurazan / Q000031:analogs & derivatives / Q000378:metabolism; D000622:Aminolevulinic Acid / Q000138:chemical synthesis / Q000737:chemistry*; D000818:Animals; D045744:Cell Line, Tumor; D005453:Fluorescence; D005944:Glucosamine / Q000031:analogs & derivatives / Q000378:metabolism; D005947:Glucose / Q000031:analogs & derivatives* / Q000737:chemistry; D006801:Humans; D008297:Male; D008647:Mesocricetus; D016513:Mice, SCID; D010693:Phloretin / Q000494:pharmacology; D010778:Photochemotherapy; D011524:Protoporphyrins / Q000378:metabolism; D051381:Rats; D025321:Surgery, Computer-Assisted
chemical_list: D011524:Protoporphyrins; C045400:6-deoxy-N-(7-nitrobenz-2-oxa-1,3-diazol-4-yl)aminoglucose; D000622:Aminolevulinic Acid; C028025:protoporphyrin IX; D009327:4-Chloro-7-nitrobenzofurazan; D005947:Glucose; D005944:Glucosamine; D010693:Phloretin