Hexylether derivative of pyropheophorbide-a (HPPH) on conjugating with 3gadolinium(III) aminobenzyldiethylenetriaminepentaacetic acid shows potential for in vivo tumor imaging (MR, Fluorescence) and photodynamic therapy.
Conjugates of 3-(1'-hexyloxyethyl)-3-devinyl pyropheophorbide-a (HPPH) with multiple Gd(III)aminobenzyl diethylenetriamine pentacetic acid (ADTPA) moieties were evaluated for tumor imaging and photodynamic therapy (PDT). In vivo studies performed in both mice and rat tumor models resulted in a significant MR signal enhancement of tumors relative to surrounding tissues at 24 h postinjection. The water-soluble (pH: 7.4) HPPH-3Gd(III) ADTPA conjugate demonstrated high potential for tumor imaging by MR and fluorescence. This agent also produced long-term tumor cures via PDT. An in vivo biodistribution study with the corresponding (14)C-analogue also showed significant tumor uptake 24 h postinjection. Toxicological evaluations of HPHH-3Gd(III)ADTPA administered at and above imaging/therapeutic doses did not show any evidence of organ toxicity. Our present study illustrates a novel approach for the development of water-soluble "multifunctional agents", demonstrating efficacy for tumor imaging (MR and fluorescence) and phototherapy.
Spernyak
Joseph A
JA
Preclinical Imaging Facility, Roswell Park Cancer Institute, Buffalo, New York 14263, USA.
White
William H
WH
Ethirajan
Manivannan
M
Patel
Nayan J
NJ
Goswami
Lalit
L
Chen
Yihui
Y
Turowski
Steven
S
Missert
Joseph R
JR
Batt
Carrie
C
Mazurchuk
Richard
R
Pandey
Ravindra K
RK
D000818:Animals; D002734:Chlorophyll / Q000031:analogs & derivatives* / Q000737:chemistry / Q000627:therapeutic use; D005453:Fluorescence; D005682:Gadolinium / Q000737:chemistry / Q000627:therapeutic use*; D008279:Magnetic Resonance Imaging / Q000379:methods; D051379:Mice; D008807:Mice, Inbred BALB C; D008809:Mice, Inbred C3H; D009369:Neoplasms / Q000175:diagnosis* / Q000188:drug therapy* / Q000473:pathology; D010778:Photochemotherapy / Q000379:methods; D051381:Rats
D002734:Chlorophyll; C083998:2-(1-hexyloxyethyl)-2-devinyl pyropheophorbide-a; D005682:Gadolinium
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