PHTHALOCYANINES AS PHOTODYNAMIC SENSITIZERS *

The most cherished goals of pharmacology are the development of selective therapeutic agents which affect exclusively the target tissue. Unfortunately, in many disorders including cancer, such a discrimination is still hard to achieve. One strategy which has been recently receiving attention is the use of compounds which acquire “drug activity” when activated by light. If such compounds are also taken up preferentially by the target tissues, selectivity is achieved by exposure to the correct wavelength of light which per se is harmless, and eventually by spatial restriction of the illumination. In this modality, for example, a photosensitizing dye restrictively confined to certain sites in the biological milieu is activated by visible light to obtain a desired effect on stained structures. A prototype of treatment belonging to this category of pharmacological agents is photodynamic therapy (PDT)t of cancer. This treatment has been based on the observation that the dye HPD, administered intravenously, as a result of some incompletely understood properties of malignant tissue, is preferentially retained in solid tumors; subsequent exposure to red light initiates a chain of events which ends in tumor necrosis. Observations that neoplastic tissues have affinity for PC were reported more than 30 years ago (Wrenn et al., 1951, Frigerio, 1962). However, only the comprehensive research of the last few years has boosted these dyes to the position of viable candidates for PDT. Several reviews on photodynamic activity of PC which have already appeared in the literature serve as a sure sign that this field has matured (Spikes, 1986; Rosenthal and Ben Hur, 1989; van Lier and Spikes, 1989; van Lier, 1990).