STRUCTURE AND BIODISTRIBUTION RELATIONSHIPS OF PHOTODYNAMIC SENSITIZERS

Photodynamic therapy (PDT) has, during the last quarter century, devel oped into a fully fledged biomedical field with its own association, t he International Photodynamic Association (TPA) and regular conference s devoted solely to this topic, Recent approval of the first PDT sensi tizer, Photofrin(R) (porfiner sodium), by health boards in Canada, Jap an, the Netherlands and United States for use against certain types of solid tumors represents, perhaps, the single most significant indicat or of the progress of PDT from a laboratory research concept to clinic al reality. The approval of Photofrin(R) will undoubtedly encourage th e accelerated development of second-generation photosensitizers, which have recently been the subject of intense study, Many of these second -generation drugs show significant differences, when compared to Photo frin(R), in terms of treatment times postinjection, light doses and dr ug doses required for optimal results, These differences can ultimatel y be attributed to variations in either the quantum efficiency of the photosensitizer in situ, which is in turn affected by aggregation stat e, localized concentration of endogenous quenchers and primary photoph ysics of the dye, or the intratumoral and intracellular localization o f the photosensitizer at the time of activation with light, The purpos e of this review is to bring together data relating to the biodistribu tion and pharmacokinetics of second-generation sensitizers and attempt to correlate this with structural and electronic features of these mo lecules, As this requires a clear knowledge of photosensitizer structu re, only chemically well-characterized compounds are included, e,g. Ph otofrin(R) and crude sulfonated phthalocyanines have been excluded as they are known to be complex mixtures, Nonporphyrin-based photosensiti zers, e,g, rose bengal and the hypericins, have also been omitted to a llow meaningful comparisons to be made between different compounds, As the intracellular distribution of photosensitizers to organelles and other subcellular structures can have a large effect on PDT efficacy, a section will be devoted to this topic.