IN-VIVO FLUORESCENCE AND PHOTODYNAMIC ACTIVITY OF ZINC PHTHALOCYANINEADMINISTERED IN LIPOSOMES

Zinc(II) phthalocyanine, a hydrophobic photosensitiser, was incorporat ed in unilamellar liposomes and studied in vivo for fluorescence kinet ics and photodynamic activity. An observation chamber mounted in a dor sal skinfold of female WAG/Rij rats was used as a model system. In the chamber, an isogeneic mammary carcinoma was transplanted in the subcu taneous tissue. Phthalocyanine fluorescence was excited at 610 nm with a power density of 0.25 mW cm(-2) and was detected above 665 nm throu gh a high-pass filter using a two-stage image intensifier coupled to a charge-coupled device (CCD) camera. Following i.v. administration of 0.14 mg kg(-1) of the drug, the fluorescence pharmacokinetics of the d ye in vasculature, normal tissue and tumour tissue was determined as a function of time. Tumour fluorescence increased slowly to a maximum a bout 3h post injection (p.i.), and remained well above the normal tiss ue fluorescence till 24h p.i. Fluorescence in the circulation was alwa ys stronger than in the tissues. A treatment light dose at a wavelengt h of 675 nm was delivered 24h p.i. One group of six animals received a total light dose of 150 J cm(-2) (100 mW cm(-2)). A second group of s ix animals received a total light dose of 450 J cm(-2) at the same dos e rate. Vascular damage resulting from treatment was observed only at the final stages of the irradiation, despite the relatively high level s of fluorescence in the circulation. Immediate post-treatment (re)tra nsplantation of the content of the chamber into the flank always resul ted in tumour regrowth, confirming the presence of viable tumour cells following photodynamic therapy (PDT). When the chamber was left intac t, the light dose of 450 J cm(-2) yielded complete tissue necrosis. Th e role of the dye-carrier complex in shielding the vascular surroundin g from photoproducts was studied in a third group of animals. The pres ence of peroxides was demonstrated in the serum of these animals after PDT with zinc phthalocyanine in liposomes (ZnPc-lip) using a total li ght dose of 450 J cm(-2). This ex vivo observation supports the previo usly reported observations in vitro that the carrier complex is able t o quench the photoproducts resulting from photoactivation of the photo sensitiser which is present in the circulation.