Showing papers by "Lina Bezdetnaya published in 2004"

Foscan®-based photodynamic treatment in vivo: correlation between efficacy and Foscan accumulation in tumor, plasma and leukocytes

Abstract: The tumoricidal effect of Foscan-mediated photodynamic therapy may involve both vessel and tumor cell destruction. The relevant importance of each mechanism seems to be defined by the time interval between photosensitizer administration and illumination (drug-light interval, DLI). Short drug-light intervals favor vascular damage due to the preferential photosensitizer accumulation in the tumor vasculature, whereas long drug-light intervals trigger direct tumor cell damage due to the dye, localization in the tumor. The purpose of this study was to investigate the influence of tumor, plasma and leukocyte concentrations of Foscan at different times after photosensitizer delivery on PDT response. Both pharmacokinetic and tumor-response studies were carried out in nude mice bearing s.c. Colo26 tumors. One to 96 h after i.v. injection of 0.5 mg/kg Foscan, animals were exposed to 10 J/cm 2 652-nm light delivered at 30 mW/cm 2 . Mean tumor regrowth time was determined for each schedule of treatment and correlated to Foscan distribution in the compartments of interest at the time of illumination. PDT efficacy was greatest for irradiations performed at 6 and 12 h post Foscan injection and limited at 96 h. Unlike tumor and plasma Foscan concentrations, photosensitizer accumulation in leukocytes exhibited a good correlation with PDT efficacy. The results suggest that leukocytes could play an important role in the mechanism of PDT-induced vascular damage either by being one of the main effector compartments or by better reflecting Foscan accumulation in endothelial cells compared to plasma. The prevalence of indirect damage was highlighted by the fact that PDT efficacy was not modified by the use of a higher fluence rate of irradiation (160 mW/cm 2 ), which depleted intratumor oxygen and did not restrain PDT-induced cell toxicity.

Photodegradation and phototransformation of 5,10,15,20-tetrakis(m-hydroxyphenyl)bacteriochlorin (m-THPBC) in solution.

Abstract: The kinetics of photobleaching and formation of photoproducts upon irradiation (735 nm) of 5,10,15,20-tetrakis(m-hydroxyphenyl)bacteriochlorin (m-THPBC) in phosphate buffer saline (PBS) supplemented with human serum albumin (HSA) were studied by means of absorption and steady-state fluorescence spectroscopy. Measurements were performed either immediately after the dye was dissolved in the HSA solution (0 h) or after six hours incubation in the HSA solution (6 h). Spectroscopic studies indicated that the dye was mainly present as aggregates in freshly prepared solutions, whereas incubation favored monomerisation. Irrespective to incubation time, the rates of photobleaching obtained by fluorescence measurements were higher than those obtained from absorbance measurements. Photobleaching of freshly prepared m-THPBC can be described by a single exponential decay, while the absorbance and fluorescence decays of the incubated dye solutions better fit a bi-exponential decay. Two photobleaching rates probably reflect differences in the photosensitivity of monomer (bound to proteins) and aggregated (non-bound) forms. Irradiation of the freshly prepared m-THPBC solution led to phototransformation of 50% of the bleached m-THPBC into 5,10,15,20-tetrakis(m-hydroxyphenyl)chlorin (m-THPC), a clinically used second generation photosensitizer. For irradiation 6 h after dissolving m-THPBC, different kinetics of m-THPC formation were found. A rapid decrease in concentration of m-THPBC was accompanied by a slow formation of m-THPC. The quantum yield of this process was small since only 5% of m-THPBC was transformed to m-THPC. The kinetics characteristics of m-THPBC photobleaching reported in the present study, together with the different kinetics of photoproduct formation during m-THPBC photobleaching, may provide important indications in the m-THPBC-based PDT dosimetry.