Structure and Biodistribution Relationships of Photodynamic Sensitizers*

Abstract

e.g. rose bengal and the hypericins, have also been omitted to allow meaningful comparisons to be made between difPhotodynamic therapy (PDT) has, during the last quarter ferent compounds. As the intracellular distribution of phocentury, into a fully fledged lieid tosensitizers to organelles and other subcellular structures with its own association, the International Photodynamic can have a large effect on PDT efficacy, a section will be Association ( P A ) and regular conferences devoted solely devoted to this topic. to this topic. Recent approval of the first PDT sensitizer, Photofrinm (porfimer sodium), by health boards in Canada, Japan, the Netherlands and United States for use against certain types of solid tumors represents, perhaps, the single most significant indicator of the progress of PDT from a laboratory research concept to clinical reality.The approval of Photofrinm will undoubtedly encourage the 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 Photofrinm, in terms of treatment times postinjection, light doses and drug doses required for optimal results. These differences can ultimately be attributed to variations in either the quantum efficiency of the photosensitizer in s h , which is in turn affected by aggregation state, localized concentration of endogenous quenchers and primary photophysics of the dye, or the intratumoral and intracellular localization of the photosensitizer at the time of activation with light. The purpose of this review is to bring together data relating to the biodistribution and pharmacokinetics of second-generation sensitizers and attempt to correlate this with structural and electronic features of these molecules. As this requires a clear knowledge of photosensitizer structure, only chemically well-characterized compounds are included, e.g. PhotofrinB and crude sulfonated phthalocyanines have been excluded as they are known to be complex mixtures. Nonporphyrin-based photosensitizers,

One- and two-photon activated phototoxicity of conjugated porphyrin dimers with high two-photon absorption cross sections

“…[9][10][11][12][13] Furthermore, the majority of commercial 30 photosensitisers show little discrimination in uptake in diseased cells vs. normal healthy tissue. 14 Both of these limitations may be reduced by exciting the photosensitiser via simultaneous two-photon absorption (TPA). Not only does two-photon excitation require near-IR light which is capable 35 of travelling further through tissues than visible light, but also the nonlinear process restricts absorption to the laser focus.…”

Photodynamic parameters in the chick chorioallantoic membrane (CAM) bioassay for topically applied photosensitizers

“…A few dozen agents are currently being evaluated for their PDT response [12,13]. The present study is limited to four compounds: sulfonated chloro-aluminum phthalocyanine (AlPcS n ) [14], benzoporphyrin derivative monoacid ring A (BPD-MA) [15,16], lutetium texaphyrin (Lutex) [17][18][19], and aminolevulinic acid (ALA), a precursor of the endogenous sensitizer protoporphyrin IX (PpIX) [20].…”

Photodynamic therapy effect of m-THPC (Foscan®) in vivo: correlation with pharmacokinetics

“…The time interval between photosensitiser administration and light delivery is crucial for the optimal clinical efficacy of PDT. The distribution of the photosensitiser both in the tumour as a whole and throughout the tumour compartments is dependent on this interval as well as in vivo interactions that affect photosensitiser aggregation, delivery and uptake (Boyle and Dolphin, 1996). m-Tetra (hydroxyphenyl)chlorin (m-THPC), a second-generation photosensitiser, has already been shown to be more potent than Photofrin (PII).…”