Photobleaching of Porphyrins Used in Photodynamic Therapy and Implications for Therapy

Abstract

Abstract— The development of an extraction procedure to quantitate dihematoporphyrin ether (DHE) concentration in tissues correlated to fluorescence measurements from instrumentation developed for in vivo fluorimetry was examined. In vivo fluorometric results from mouse mammary carcinoma (SMT‐F) were calibrated against results of the chemical extraction assay quantitated spectrophotometrically. Fluorescence and drug extractable levels increase in a linear fashion with injected dose. Loss of porphyrin fluorescence (photobleaching) and intra‐tumoral porphyrin level has been demonstrated both in vitro (NHIK cells) and in vivo (SMT‐F tumor) during illumination with light following exposure to Hpd or DHE. This process is essentially independent of porphyrin tumor level in vivo and could lead to tumor protection at very low porphyrin levels. On the other hand, this photobleaching process which occurs concurrent with cellular inactivation and tissue damage due to the photodynamic process can be exploited to protect normal tissue during photodynamic therapy (PDT) and thus greatly enhance the therapeutic ratio. This has been demonstrated in patients undergoing PDT.

Validation of Photodynamic Action via Photobleaching of a New Curcumin-Based Composite with Enhanced Water Solubility

“…This fact occurs due to the short lifetime of the formed reactive species. This photobleaching reduces the PDT efficiency and its outcome [33]. The formation of oxidative chemical species is also the principle of the photodynamic action.…”

Halogen atom effect on photophysical and photodynamic characteristics of derivatives of 5,10,15,20-tetrakis(3-hydroxyphenyl)porphyrin

“…The photobleaching of the sensitizer in photodynamic therapy has received increasing attention because sensitizer destruction could be a limiting factor of its activity [33,34]. Our sensitizers show very different photobleaching rates, varying with the nature and number of halogen atoms.…”

Time‐resolved Luminescence Spectroscopy of Photosensitizers of Biomedical Interest*

“…Though it is common use to call the corresponding clinical procedure photodynamic therapy (PDT), it has still to be proved that type I1 mechanisms are the only basis of the cytotoxic reactions that eventually lead to cell death (Parker, 1987). In contrast, type I1 reactions alone would not account for the photodegradation of porphyrins observed both during PDT (Mang et al, 1987) and during cell photosensitization (Schneckenburger et al, 1984).…”