Pyropheophorbide 2-deoxyglucosamide: a new photosensitizer targeting glucose transporters.
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.
Zhang
Min
M
Department of Radiology, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA.
Zhang
Zhihong
Z
Blessington
Dana
D
Li
Hui
H
Busch
Theresa M
TM
Madrak
Vanessa
V
Miles
Jeremy
J
Chance
Britton
B
Glickson
Jerry D
JD
Zheng
Gang
G
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
D009004:Monosaccharide Transport Proteins; D017319:Photosensitizing Agents; C482914:pyropheophorbide 2-deoxyglucosamide; D003847:Deoxyglucose