In vivo fluorescence kinetics of phthalocyanines in a skin-fold observation chamber model: role of central metal ion and degree of sulfonation.

The fluorescence pharmacokinetics of a series of metallosulfophthalocyanines, chelated with either aluminum or zinc and sulfonated to different degrees, was studied by fluorescence measurements in vivo. Dyes were administered systemically to female WAG/RIJ rats with an isogeneic mammary carcinoma transplanted into the subcutis in a transparent observation chamber located on their backs. Following an intravenous injection of 2.5 mumol/kg of the dye, fluorescence dynamics was observed up to 7 h postinjection. The phthalocyanines were excited at 610 nm with a power density of 0.1 mW/cm2 without causing photodynamic damage to the vasculature. Fluorescence was detected above 665 nm using a fluorescence imaging system based on an image intensifier. Dye retention in the blood vessels and tumor tissue was expressed as ratios relative to the fluorescence signal of the surrounding subcutaneous tissue. Phthalocyanines chelated with aluminum gave the highest fluorescence signal with tumor-over-subcutis ratios of up to a value of 4. The zinc complexes exhibited the highest vascular-over-subcutis ratios with maximum values exceeding a value of 6. They also displayed the longest retention times in the vascular system of well over 7 h. Overall, decreasing the degree of sulfonation of the metallophthalocyanines results in lower tumor-over-normal tissue fluorescence ratios, and furthermore aluminum-based dyes seem superior tumor localizers over zinc-based dyes. The advantages of phthalocyanines over porphyrins with respect to tumor localization and photodynamic therapy are discussed.