In vivo stability and photodynamic efficacy of fluorinated bacteriopurpurinimides derived from bacteriochlorophyll-a.
The stable bacteriopurpurinimide (788 nm, epsilon: 38,600 in CH2Cl2), obtained by reducing the corresponding unstable Schiff base (803 nm, epsilon: 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 micromol/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.
Photodynamic Therapy Center, Department of Dermatology, Roswell Park Cancer Institute, and Institute for Lasers, Photonics and Biophotonics, SUNY at Buffalo, Buffalo, New York 14260, USA.
Amy L
AL
Gryshuk
Yihui
Y
Chen
William
W
Potter
Tymish
T
Ohulchansky
Allan
A
Oseroff
Ravindra K
RK
Pandey
D000818:Animals; D025541:Bacteriochlorophyll A / Q000737:chemistry*; D001596:Benzylamines / Q000737:chemistry; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D002851:Chromatography, High Pressure Liquid; D004355:Drug Stability; D005260:Female; D005354:Fibrosarcoma / Q000188:drug therapy; D005461:Fluorine; D007094:Imides / Q000138:chemical synthesis* / Q000494:pharmacology; D051379:Mice; D009381:Neoplasms, Radiation-Induced / Q000188:drug therapy; D010084:Oxidation-Reduction; D010778:Photochemotherapy; D017319:Photosensitizing Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology; D011166:Porphyrins / Q000138:chemical synthesis* / Q000493:pharmacokinetics / Q000494:pharmacology; D012867:Skin / Q000098:blood supply / Q000187:drug effects / Q000528:radiation effects
D025541:Bacteriochlorophyll A; D001596:Benzylamines; D007094:Imides; D017319:Photosensitizing Agents; D011166:Porphyrins; C059051:purpurin 18; D005461:Fluorine