Comparison of meso-tetrahydroxyphenyl-chlorin and meso-tetrahydroxyphenyl-bacteriochlorin with respect to photobleaching and PCT efficiency in vivo

摘要

Abstract: Using BALB/c nude mice bearing WiDr human colon adenocarcinoma, we investigated photobleaching and photochemotherapeutic (PCT) effects of meso- tetrahydroxyphenyl-chlorin (mTHPC) and meso- tetrahydroxyphenyl-bacteroiochlorin (mTHPBC). For both studies, mice were injected i.p. 1 mg/kg mTHPC and mTHPBC, respectively, 24 hr before light irradiation. Photobleaching of the sensitizers in mouse skin was carried out using a dye laser (for mTHPC) and 1 KW xenon source equipped with a monochromator (for mTHPBC). Fluorescence measurements were made by means of a fiberoptic system, exciting and collecting the fluorescence from the mouse skin. The system was coupled to a PE L550 fluorimeter. For the PCT study, the mTHPC or mTHPBC-sensitized tumors were exposed to the laser at a fluence of 10 J/cm$+2$/. The responses of the treated tumors were evaluated by measuring the tumor growth. We found that both mTHPC and mTHPBC are photolabile. Approximately 80% of the fluorescence of the two dyes in the mouse skin is bleached by a fluence of 10 J/cm$+2$/. When mTHPBC in mouse skin was photobleached by light of 740 nm, the bacteriochlorin (peak at 740 nm) was significantly bleached while the chlorin (peak at 652 nm) was unaffected. The growth of the tumors was delayed by 13 days after PCT with 1 mg/kg mTHPC Irradiation at 652 nm) and 5 days delay after PCT with 1 mg/kg mTHPBC (irradiation at 515 nm). The present data indicate that (1) by proper choice of a low dose of mTHPC or MTHPBC, it is possible to photobleach the sensitizers in normal tissues without eliminating their PCT effect on tumor tissues; (2) in order to increase the efficiency of PCT with mTHPBC, fractionated irradiation with different wavelengths (740 nm and 652 nm) should be considered to be used. !5