title: Pyropheophorbide 2-deoxyglucosamide: a new photosensitizer targeting glucose transporters.
abstract: To prepare near-infrared fluorescence imaging and photodynamic therapy agents targeted at glucose transporters, pyropheophorbide 2-deoxyglucosamide (Pyro-2DG) was synthesized and evaluated in a 9L glioma rat model. Fluorescence imaging studies demonstrate that Pyro-2DG is selectively accumulated in the tumor. Upon its photoactivation, we demonstrate that this agent efficiently causes selective mitochondrial damage to the region of a tumor that was photoirradiated after administration of this agent, but does not affect tissues photoirradiated in the absence of the agent or tissues treated with the agent that are not photoirradiated. Preliminary confocal microscopy studies suggest that Pyro-2DG is delivered and trapped in tumor cells via the GLUT/hexokinase pathway and therefore is useful both as a tumor-targeted NIR fluorescence imaging probe and as a PDT agent for the destruction of cancer.
authors.affiliation: Department of Radiology, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA.
authors.forename: Min
authors.initials: M
authors.lastname: Zhang
authors.forename: Zhihong
authors.initials: Z
authors.lastname: Zhang
authors.forename: Dana
authors.initials: D
authors.lastname: Blessington
authors.forename: Hui
authors.initials: H
authors.lastname: Li
authors.forename: Theresa M
authors.initials: TM
authors.lastname: Busch
authors.forename: Vanessa
authors.initials: V
authors.lastname: Madrak
authors.forename: Jeremy
authors.initials: J
authors.lastname: Miles
authors.forename: Britton
authors.initials: B
authors.lastname: Chance
authors.forename: Jerry D
authors.initials: JD
authors.lastname: Glickson
authors.forename: Gang
authors.initials: G
authors.lastname: Zheng
mesh_terms: D000818:Animals; D003847:Deoxyglucose / Q000031:analogs & derivatives / Q000138:chemical synthesis / Q000493:pharmacokinetics / Q000494:pharmacology*; D005910:Glioma / Q000378:metabolism / Q000473:pathology / Q000532:radiotherapy; D008297:Male; D018613:Microscopy, Confocal; D008956:Models, Chemical; D009004:Monosaccharide Transport Proteins / Q000032:analysis / Q000187:drug effects / Q000378:metabolism*; D010778:Photochemotherapy / Q000379:methods; D017319:Photosensitizing Agents / Q000138:chemical synthesis / Q000493:pharmacokinetics / Q000494:pharmacology*; D051381:Rats; D011916:Rats, Inbred F344; D013050:Spectrometry, Fluorescence; D019265:Spectroscopy, Near-Infrared
chemical_list: D009004:Monosaccharide Transport Proteins; D017319:Photosensitizing Agents; C482914:pyropheophorbide 2-deoxyglucosamide; D003847:Deoxyglucose