6 July 1999 Transport, localization, and phototoxicity of m-THPC
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Proceedings Volume 3592, Optical Methods for Tumor Treatment and Detection: Mechanisms and Techniques in Photodynamic Therapy VIII; (1999); doi: 10.1117/12.351504
Event: BiOS '99 International Biomedical Optics Symposium, 1999, San Jose, CA, United States
Abstract
Since the photosensitizing agent mTHPC is insoluble in water, a formulation procedure, usually involving poly(ethylene glycol) and ethanol, is required for clinical and pre-clinical studies. Using this vehicle, we found that drug accumulation by murine leukemia L1210 cells in vitro was slow; only non-viable cells with damaged membranes showed rapid uptake of mTHPC. The drug ultimately localized in the cytosol, and subsequent irradiation led to mitochondrial > lysosomal >> membrane photodamage, and a rapid apoptotic response. The rate-limiting step in drug accumulation appears to involve dissociation of a transient albumin-bound aggregated species which exhibited a low fluorescence yield. Initial formation of this product may explain the unusual mTHPC pharmacokinetics in man recently reported. Dilution of mTHPC with human plasma led to a gradual increase in fluorescence yield as the drug became associated with lipoproteins and proteins. When a steady-state was reached, density-gradient ultracentrifugation indicated distribution of mTHPC to HDL > LDL >> albumin.
© (1999) COPYRIGHT Society of Photo-Optical Instrumentation Engineers (SPIE). Downloading of the abstract is permitted for personal use only.
David Kessel, Elizabeth Sykes, "Transport, localization, and phototoxicity of m-THPC", Proc. SPIE 3592, Optical Methods for Tumor Treatment and Detection: Mechanisms and Techniques in Photodynamic Therapy VIII, (6 July 1999); doi: 10.1117/12.351504; https://doi.org/10.1117/12.351504
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KEYWORDS
Luminescence

Plasma

Bioalcohols

Proteins

Photodynamic therapy

Adaptive optics

Biological research

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