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    Due to the increasing complexity very precise evaluation of the effective delivered dose in PDT seems today hardly reachable challenge. Although the use of photosensitizer photobleaching in implicit dosimetry is attractive in principle, there are a number of problems which must be resolved for it to become routinely useful. We have tried to add few additional aspects related to photobleaching of sensitizer as dose metrics, which is widely discussed in the paper of Wilson et al [1].
It is necessary to know the degree of photosensitizer coupling in the specific tissue environment, which may depend on factor such as the specific photosensitizer binding to the tissue substrate. Localization in different compartments and binding with different biomolecules can alter not only sensitization properties of sensitizer but also the photobleaching rate and photoproduct formation efficacy.

    Other factor, which may have significant influence on the use of photobleaching as dose metrics, is pH of the environment. This is especially important for photosensitizers preferentially localizing in lysosomes. The lower pH can increase the photostability of sensitizer and change the coupling of the photobleaching with biological effect.
It also should be stressed that low fluorescence of photoproduct does not reflect the efficacy of photosensitization process. Moreover, it shows that less energy absorbed by sensitizer is lost by fluorescence and more might be used for the population of triplet state and as a consequence for the generation of photodynamically active species.
Today we have not any easy usable method to evaluate the biochemical and physiological tissue response to PDT and to correlate with the effective delivered dose. Therefore, in spite of all mentioned and not mentioned shortages, the use of photophysical characteristics as an index of effective delivered dose to date seems to be the most reliable parameter.


This work in part was supported by the Lithuanian State Science and Education Foundation and the Norwegian Research Council. S.B. and J.P. are indebted to Prof.J.Moan for the opportunity to perform experiments with ALA-induced porphyrins in his lab and for the fruitful discussions.