Photophysical Parameters, Photosensitizer Retention and Tissue Optical Properties Completely Account for the Higher Photodynamic Efficacy of meso-Tetra-Hydroxyphenyl-Chlorin vs Photofrin

Authors

  • Soumya Mitra,

    1. Department of Radiology, University of Rochester, 601 Elmwood Avenue, Box 648, Rochester, NY
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  • Thomas H. Foster

    Corresponding author
    1. Department of Radiology, University of Rochester, 601 Elmwood Avenue, Box 648, Rochester, NY
      *To whom correspondence should be addressed: Department of Radiology, University of Rochester, 601 Elmwood Avenue, Box 648, Rochester, NY 14642, USA. Fax: 585-273-1033; e-mail: thomas.foster@rochester.edu
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  • Posted on the website on 4 April 2005

*To whom correspondence should be addressed: Department of Radiology, University of Rochester, 601 Elmwood Avenue, Box 648, Rochester, NY 14642, USA. Fax: 585-273-1033; e-mail: thomas.foster@rochester.edu

ABSTRACT

Meso-tetra-hydroxyphenyl-chlorin (mTHPC) is one of the most potent photosensitizers currently available for clinical photodynamic therapy (PDT). However the reason or reasons for its high photodynamic efficacy remain(s) unresolved. To investigate the PDT efficacy of mTHPC vs Photofrin we use the knowledge of photophysical parameters extracted from the analysis of oxygen electrode measurements in spheroids to compute and compare their respective singlet oxygen (1O2 dose depositions. The electrode measurements indirectly report the bleaching kinetics of mTHPC and indicate that its photobleaching mechanism is consistent with 1O2-mediated reactions. mTHPC's photodegradation via1O2 reactions is confirmed by a more direct evaluation of the spatially resolved fluorescence in confocal sections of intact spheroids during irradiation. The PDT efficacy comparisons establish that mTHPC's enhanced potency may be accounted for completely on the basis of its ability to sequester tightly in cells and its photophysical properties, in particular its higher extinction coefficient at a redshifted wavelength. We extend the efficacy comparison to include the influence of hemoglobin absorption of PDT treatment light and show that incorporating the influence of wavelength-dependent light attenuation in tissue further contributes to significantly higher efficacy for mTHPC- vs Photofrin-PDT.

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