In Vivo Stability and Photodynamic Efficacy of Fluorinated Bacteriopurpurinimides Derived from Bacteriochlorophyll-a

J. Med. Chem., 49 (6), 1874 -1881, 2006. 10.1021/jm050919z S0022-2623(05)00919-2
Web Release Date: February 18, 2006

In Vivo Stability and Photodynamic Efficacy of Fluorinated Bacteriopurpurinimides Derived from Bacteriochlorophyll-a

Amy L. Gryshuk, Yihui Chen, William Potter, Tymish Ohulchansky, Allan Oseroff,* and Ravindra K. Pandey*

Photodynamic Therapy Center, Department of Dermatology, and Department of Nuclear Medicine/Radiology, Roswell Park Cancer Institute, Buffalo, New York 14263, and Institute for Lasers, Photonics and Biophotonics, SUNY at Buffalo, Buffalo, New York 14260

Received September 16, 2005

Abstract:

The stable bacteriopurpurinimide (788 nm, : 38 600 in CH₂Cl₂), obtained by reducing the corresponding unstable Schiff base (803 nm, : 50 900 in CH₂Cl₂) that was isolated by reacting bacteriopurpurin methyl ester with 3,5-bis-(trifluoromethyl)benzylamine, produced promising photosensitizing efficacy. ¹H NMR, mass spectrometry, and HPLC analyses confirmed the structures of new bacteriopurpurinimides and the metabolic product. The preliminary in vivo photosensitizing efficacy of this stable bacteriopurpurinimide was determined in C3H mice bearing radiation induced fibrosarcoma tumors as a function of variable drug doses. A drug dose of 1.0 mol/kg and light exposure of 135 J/cm² (75 mW/cm²; 24 h postinjection) at 796 nm for 30 min produced a 60% long-term tumor cure (3/5 mice were tumor-free on day 90). Colocalization study of the stable bacteriopurpurinimide with MitoTracker Green confirmed some mitochondrial localization. The fluorescein-exclusion assay and histological staining of CD31 confirmed vascular stasis at various time points post-PDT (post photodynamic therapy). The treatment parameters (time for maximum drug uptake and wavelength for light irradiation) were determined by in vivo reflectance spectroscopy.

Download the full text: PDF | HTML