New Sensitizers for Photodynamic Therapy of Cancer

Abstract

The sensitizer preparations currently used in clinical trials of photodynamic therapy (PDT) of cancer (Dougherty, 1987) consist of mixtures of hematoporphyrin derivatives (HPD) obtained via alkaline hydrolysis of hematoporphyrin acetates (Lipson et al., 1961; Bonnett et al., 1981). Although the different components of HPD all exhibit good in vitro photodynamic properties, only the aggregated fraction of HPD is sufficiently retained by neoplasms to exhibit in vivo photodynamic action. This active component of HPD has been labeled DHE and is characterized as a mixture of dihematoporphyrins and oligomers containing 2–5 hematoporphyrin (HP) units (Kessel, 1987) linked via ether and ester bonds (Dougherty et al., 1984; Kessel, 1986a). It has recently been shown by Kessel (1987) that both ester and ether linked material localizes in tumors and furthermore, that upon storage hydrolysis of the ester bonds occurs resulting in enrichment of ether linked hematoporphy- rins in the DHE fraction. In view of the increased understanding of the chemical nature of the active components of HPD several attempts have been made to rationalize the preparation of DHE. The development of photosensitizers with improved photochemical.properties is also actively pursued. Hematoporphyrins absorb only weakly above 600 nm (Fig. 1), where light exhibits optimal penetration through tissue, and several porphin analogs with re-shifted absorption maxima as compared to DHE are at present under evaluation as alternative photosensitizers for PDT.