The Foster Research Group
Fluorescence Photobleaching and Photoproduct Formation
Representative publications
J.C. Finlay, D.L. Conover, E.L. Hull, and T.H. Foster. Porphyrin bleaching and PDT-induced spectral changes are irradiance dependent in ALA-sensitized normal rat skin in vivo. Photochem. Photobiol. 73, 54-63 (2001).
J.C. Finlay, S. Mitra, and T.H. Foster. In vivo mTHPC photobleaching in normal rat skin exhibits unique irradiance dependent features. Photochem. Photobiol. 75, 282-288 (2002).
J.C. Finlay, S. Mitra, M.S. Patterson, and T.H. Foster. Photobleaching kinetics of Photofrin in vivo and in multicell tumor spheroids indicate two simultaneous bleaching mechanisms. Phys. Med. Biol. 49, 4837-4860 (2004).
W.J. Cottrell, A.R. Oseroff, andT.H. Foster. A portable instrument that integrates irradiation with fluorescence and reflectance spectroscopies during clinical photodynamic therapy of cutaneous disease. Rev. Sci. Instrum. 77, 064302 (2006).
Most photosensitizers used in photodynamic therapy are chemically modified by the photochemistry that they initiate. These modifications may take the form of photoproducts with fluorescence spectra that differ from that of the parent compound, and/or the irreversible photobleaching of the sensitizer, which gives rise to a progressive loss of fluorescence during irradiation. Thus, these modifications in fluorescence report something about the local photochemistry in the cells or tissue undergoing PDT. For this reason, monitoring sensitizer photobleaching and photoproduct accumulation during treatment has received some attention as a possible surrogate reporter of photodynamic dose deposition and biological response. We have been very active in this area during the past several years. In particular, we have been interested in the irradiance dependence of photobleaching/photoproduct formation because in a number of model systems the biological response to PDT shows a strong such dependence.
Spectra acquired in an intact spheroid incubated with h-ALA for 3 hours. Contributions from PpIX and photoproducts are shown for spectra acquired pre- and post-PDT in different regions of the spheroid.
Our work on sensitizer photobleaching has resulted in several publications. Jarod Finlay et al. reported on interesting irradiance-dependent features of the fluorescence spectra of ALA-induced PpIX and its photoproducts (2001) and on the irradiance dependence of the bleaching of mTHPC (2002), which does not form a photoproduct. Experiments with Photofrin revealed a complex situation, in which Photofrin bleaching in vivo and in multicell tumor spheroids was mediated by a “mixed” singlet-oxygen and excited-triplet-state mechanism. The irradiance dependence of the Photofrin photoproduct accumulation, however, was consistent with a singlet-oxygen-mediated mechanism (Finlay et al., 2004). Recently, we designed and built an instrument that integrates the delivery of PDT irradiation with the acquisition of fluorescence and reflectance spectra during therapy (Cottrell et al., 2006). This device is now part of a clinical trial of ALA-PDT in the treatment of human superficial basal cell carcinoma at nearby Roswell Park Cancer Institute. The fluorescence spectroscopy results of this study are critical in determining the choice of optimal irradiation parameters for a future trial of low-irradiance PDT in this patient population.