IN-VIVO PHOTODYNAMIC EFFECTS OF PHTHALOCYANINES IN A SKIN-FOLD OBSERVATION CHAMBER MODEL - ROLE OF CENTRAL METAL-ION AND DEGREE OF SULFONATION

Six sulfonated metallophthalocyanines, chelated with either aluminum o r zinc and sulfonated to different degrees, were studied in vivo for t heir photodynamic activity in a rat skin-fold chamber model. The chamb er, located on the back of female WAG/Rij rats, contained a syngeneic mammary carcinoma implanted into a layer of subcutaneous tissue. Twent y-four hours after intravenous administration of 2.5 mumol/kg of one o f the dyes, the chambers received a treatment light dose of 600 J/cm2 with monochromatic light of 675 nm at a power density of 100 mW/cm2. D uring light delivery and up to a period of 7 days after treatment, vas cular effects of tumor and normal tissue were scored. Tumor cell viabi lity was determined by histology and by reimplantation of the chamber contents into the skin of the same animal, either 2 h after treatment or after the 7 day observation period. Vascular effects of both tumor and subcutaneous tissue were strongest with dyes with the lowest degre e of sulfonation and decreased with increasing degree of sulfonation. Tumor regrowth did not occur with aluminum phthalocyanine mono- and di sulfonate and with zinc phthalocyanine monosulfonate. With the protoco l that was used, complete necrosis without recovery was only observed when reimplantation took place at the end of the 7 day follow-up perio d. Reimplantation 2 h after treatment always resulted in tumor regrowt h. At this interval, the presence of viable tumor cells was confirmed histologically. In general tumor tissue vasculature was more susceptib le to photodynamic damage than vasculature of the normal tissue. The e ffect on the circulation of both tumor and normal tissue increased wit h decreasing degree of sulfonation. Based on this study, the photodyna mic effects using the six sulfonated metallophthalocyanines on the vas culature can be ranked from high to low as: AlPcS2 almost-equal-to ZnP cS1 > AlPcS1 > AlPcS4 > ZnPcS2 > ZnPcS4.