Effects of Fluence Rate on Cell Survival and Photobleaching in Meta-Tetra-(hydroxyphenyl)chlorin–photosensitized Colo 26 Multicell Tumor Spheroids

We report the influence of fluence rate on the photobleaching and cell survival in Colo 26 multicell spheroids photosensitized by meta-tetra-(hydroxyphenyl)chlorin (mTHPC). Photosensitizer degradation and therapeutic efficacy increased dramatically and progressively when the fluence rate was reduced...

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Veröffentlicht in:Photochemistry and photobiology 2001-03, Vol.73 (3), p.297-303
Hauptverfasser: Coutier, Stéphanie, Mitra, Soumya, Bezdetnaya, Lina N., Parache, Robert M., Georgakoudi, Irene, Foster, Thomas H., Guillemin, François
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container_end_page 303
container_issue 3
container_start_page 297
container_title Photochemistry and photobiology
container_volume 73
creator Coutier, Stéphanie
Mitra, Soumya
Bezdetnaya, Lina N.
Parache, Robert M.
Georgakoudi, Irene
Foster, Thomas H.
Guillemin, François
description We report the influence of fluence rate on the photobleaching and cell survival in Colo 26 multicell spheroids photosensitized by meta-tetra-(hydroxyphenyl)chlorin (mTHPC). Photosensitizer degradation and therapeutic efficacy increased dramatically and progressively when the fluence rate was reduced over the range from 90 to 5 mW cm−2. These experimental results were compared to a mathematical model of photobleaching based on self-sensitized singlet oxygen reactions with the photosensitizer ground state. This model incorporates photophysical parameters obtained from microelectrode measurements of oxygen depletion at the surface of mTHPC-sensitized spheroids and was refined by including the inhomogeneous distribution of mTHPC in spheroids and oxygen depletion in the bulk medium. Since the model is consistent with the experimental data we conclude that the fluence rate dependence of the cell survival and of mTHPC photobleaching is due to photochemical oxygen consumption and a predominantly singlet oxygen-mediated mechanism of mTHPC photobleaching. The threshold dose of reacting singlet oxygen was calculated to be 7.9 ± 2.2 mM in this system.
doi_str_mv 10.1562/0031-8655(2001)073<0297:EOFROC>2.0.CO;2
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Photosensitizer degradation and therapeutic efficacy increased dramatically and progressively when the fluence rate was reduced over the range from 90 to 5 mW cm−2. These experimental results were compared to a mathematical model of photobleaching based on self-sensitized singlet oxygen reactions with the photosensitizer ground state. This model incorporates photophysical parameters obtained from microelectrode measurements of oxygen depletion at the surface of mTHPC-sensitized spheroids and was refined by including the inhomogeneous distribution of mTHPC in spheroids and oxygen depletion in the bulk medium. Since the model is consistent with the experimental data we conclude that the fluence rate dependence of the cell survival and of mTHPC photobleaching is due to photochemical oxygen consumption and a predominantly singlet oxygen-mediated mechanism of mTHPC photobleaching. 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subjects Animals
Cell Survival - drug effects
Cell Survival - radiation effects
Colorectal Neoplasms - metabolism
Colorectal Neoplasms - pathology
Mesoporphyrins - metabolism
Mesoporphyrins - pharmacology
Mice
PHOTOMEDICINE
Photosensitizing Agents - metabolism
Photosensitizing Agents - pharmacology
Tumor Cells, Cultured
title Effects of Fluence Rate on Cell Survival and Photobleaching in Meta-Tetra-(hydroxyphenyl)chlorin–photosensitized Colo 26 Multicell Tumor Spheroids
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