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Temporally and Spatially Heterogeneous Distribution of mTHPC in a Murine Tumor Observed by Two‐color Confocal Fluorescence Imaging and Spectroscopy in a Whole‐mount Model
Author(s) -
Mitra Soumya,
Maugain Estelle,
Bolotine Lina,
Guillemin Francois,
Foster Thomas H.
Publication year - 2005
Publication title -
photochemistry and photobiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.818
H-Index - 131
eISSN - 1751-1097
pISSN - 0031-8655
DOI - 10.1562/2005-03-24-ra-471
Subject(s) - photodynamic therapy , photosensitizer , confocal , fluorescence , confocal microscopy , distribution (mathematics) , fluorescence lifetime imaging microscopy , chemistry , biophysics , drug delivery , verteporfin , pathology , biomedical engineering , medicine , biology , biochemistry , photochemistry , optics , mathematical analysis , physics , mathematics , organic chemistry , choroidal neovascularization , microbiology and biotechnology , retinal
Efficient intratumor delivery of anticancer drugs and photo‐sensitizers is an important factor in the success of chemotherapy and photodynamic therapy, respectively. Unfortunately, their adequate and uniform intratumor distribution is impeded by several physiological barriers and by binding to tissue components. Measurement of gross tumor drug accumulation is a routine method of investigating the uptake and clearance of chemotherapy agents and photosensitizers but tells little about their extravascular spatial distribution. We use whole‐mount two‐color confocal fluorescence imaging and imaging spectroscopy of unprocessed excised murine tumor fragments to investigate the intratumor distribution of the photosensitizer meso‐tetrahydroxyphenyl chlorin (mTHPC) as a function of distance from blood vessels perfused with 0.2 μm diameter fluorescent microspheres. Significant mismatches between drug and perfused vasculature are caused by heterogeneities in tumor blood supply. We describe complex microscopic mTHPC gradients that reverse dramatically relative to the perfused vasculature with time after injection. This imaging technique can be applied to screen the dynamic intratumor distribution of other fluorescent photosensitizers and anticancer drugs.