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.

Abstract

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.

• Authors: Joseph A Spernyak, William H White 3rd, Manivannan Ethirajan, Nayan J Patel, Lalit Goswami, Yihui Chen, Steven Turowski, Joseph R Missert, Carrie Batt, Richard Mazurchuk, Ravindra K Pandey
• Journal: Bioconjugate chemistry (Bioconjug Chem) Vol. 21 Issue 5 Pg. 828-35 (May 19 2010) ISSN: 1520-4812 [Electronic] United States
• PMID: 20387862 (Publication Type: Journal Article, Research Support, N.I.H., Extramural)

Chemical References

• Chlorophyll
• 2-(1-hexyloxyethyl)-2-devinyl pyropheophorbide-a
• Gadolinium

Topics

• Animals
• Chlorophyll (analogs & derivatives, chemistry, therapeutic use)
• Fluorescence
• Gadolinium (chemistry, therapeutic use)
• Magnetic Resonance Imaging (methods)
• Mice
• Mice, Inbred BALB C
• Mice, Inbred C3H
• Neoplasms (diagnosis, drug therapy, pathology)
• Photochemotherapy (methods)
• Rats