CORRELATION OF DISTRIBUTION OF SULFONATED ALUMINUM PHTHALOCYANINES WITH THEIR PHOTODYNAMIC EFFECT IN TUMOR AND SKIN OF MICE BEARING CAD2 MAMMARY-CARCINOMA

A chemical extraction assay and fluorescence microscopy incorporating a light-sensitive thermoelectrically cooled charge-coupled device (CCD) camera was used to study the kinetics of uptake, retention and localisation of disulphonated aluminium phthalocyanine (AlPcS(2)) and tetrasulphonated aluminium phthalocyanine (AlPcS(4)) at different time intervals after an i.p. injection at a dose of 10 mg kg(-1) body weight (b.w.) in tumour and surrounding normal skin and muscle of female C3D2/F-1 mice bearing CaD2 mammary carcinoma. Moreover, the photodynamic effect on the tumour and normal skin using sulphonated aluminium phthalocyanines (AlPcS(1), AlPcS(2), AlPcS(4)) and Photofrin was compared with respect to dye, dye dose and time interval between dye administration and light exposure. The maximal concentrations of AlPcS(2) in the tumour tissue were reached 2-24 h after injection of the dye, while the amounts of AlPcS(4) peaked l-ih after the dye administration. AlPcS(2) was simultaneously localised in the interstitium and in the neoplastic cells of the tumour, whereas AlPcS(4) appeared to localise only in the stroma of the tumour. The photodynamic efficiency (light was applied 24 h after dye injection at a dose of 10 mg kg(-1) b.w.) of the rumours was found to decrease in the following order: AlPcS(2) > AlPcS(4) > Photofrin > AlPcS(1). Furthermore, photodynamic efficacy was strongly dependent upon dye doses and time intervals between dye administration and light exposure: the higher the dose, the higher the photodynamic efficiency. The most efficient photodynamic therapy (PDT) of the tumour was reached (day 20 tumour-free) when light exposure took place 2 h after injection of AlPcS(2) (10 mg kg(-1)). A dual intratumoral localisation pattern of the dye, as found for AlPcS(2), seems desirable to obtain a high photodynamic efficiency. The kinetic patterns of uptake, retention and localisation of AlPcS(2) and AlPcS(4) are roughly correlated with their photodynamic effect on the tumour and normal skin.