Photobleaching kinetics of Photofrinin vivoand in multicell tumour spheroids indicate two simultaneous bleaching mechanisms
- 9 October 2004
- journal article
- Published by IOP Publishing in Physics in Medicine & Biology
- Vol. 49 (21), 4837-4860
- https://doi.org/10.1088/0031-9155/49/21/001
Abstract
We present a detailed investigation of Photofrin photobleaching and photoproduct accumulation. Fisher rats were sensitized with 10 mg kg(-1) Photofrin and irradiated 24 h later with 514 nm light at 5 or 100 mW cm(-2). Fluorescence spectra were collected from the skin throughout treatment, and sensitizer bleaching and fluorescent photoproduct formation were quantified using spectral analysis. Photofrin bleaching was slightly more rapid at the higher irradiance under these conditions. However, accumulation of photoproduct was significantly enhanced at lower irradiance. To interpret these unexpected findings, we developed a new mathematical model in which reactions between singlet oxygen (1O2) and the photosensitizer and reactions between the sensitizer triplet and biological targets are both allowed to contribute to bleaching. Predictions of this model were tested in experiments performed on EMT6 spheroids sensitized with concentrations of 2.5, 10 and 30 microg mL(-1) Photofrin and subjected to PDT. Photofrin bleaching and photoproduct formation in these spheroids were measured using confocal fluorescence spectroscopy. In qualitative agreement with the mixed-mechanism model predictions, at the highest drug concentration Photofrin bleaching was more efficient via 1O2 reactions, while at the lowest concentration triplet reactions were more efficient. At all concentrations, photoproduct accumulation was greater under conditions of abundant oxygen.Keywords
This publication has 18 references indexed in Scilit:
- The Mechanism of Photofrin Photobleaching and Its Consequences for Photodynamic DosimetryPhotochemistry and Photobiology, 1997
- A recipe for the preparation of a rodent food that eliminates chlorophyll-based tissue fluorescenceJournal of Photochemistry and Photobiology B: Biology, 1995
- Uptake and distribution of intravenously or intravesically administered photosensitizers in the ratCancer Letters, 1993
- QUANTUM YIELDS AND KINETICS OF THE PHOTOBLEACHING OF HEMATOPORPHYRIN, PHOTOFRIN II, TETRA(4-SULFONATOPHENYL)-PORPHINE AND UROPORPHYRINPhotochemistry and Photobiology, 1992
- Oxygen Consumption and Diffusion Effects in Photodynamic TherapyRadiation Research, 1991
- Photoproducts formed from photofrin II in cellsJournal of Photochemistry and Photobiology B: Biology, 1988
- PHOTOBLEACHING OF PHOTOFRIN II AS A MEANS OF ELIMINATING SKIN PHOTOSENSITIVITY*Photochemistry and Photobiology, 1987
- THE THEORY OF PHOTODYNAMIC THERAPY DOSIMETRY: CONSEQUENCES OF PHOTO-DESTRUCTION OF SENSITIZERPhotochemistry and Photobiology, 1987
- PHOTOBLEACHING OF PORPHYRINS USED IN PHOTODYNAMIC THERAPY AND IMPLICATIONS FOR THERAPYPhotochemistry and Photobiology, 1987
- Effect of bleaching of porphyrin sensitizers during photodynamic therapyCancer Letters, 1986