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All photosensitizers applied in experimental- and clinical-photochemotherapy (PCT) have broad absorption spectra stretching from the ultraviolet up to 6 - 700 nm. Light of wavelengths in the red part of the spectrum is chosen for PCT even though the extinction coefficients of the sensitizers are usually smaller in this wavelength region than at shorter wavelengths. Thus, if one wants to treat superficial tumors or skin disorders, this may be a wrong choice. Two pieces of information are needed in order to make a proper choice of wavelength to treat a lesion of a given depth: the wavelength dependence of the optical penetration depth into tissue, and the action spectrum for tumor destruction. Additionally, the skin photosensitivity induced by the drug should be considered. We have non-invasively measured the optical penetration spectra of human tissues in vivo and the fluorescence excitation spectra for several sensitizers, including protoporphyrin (PpIX), in cells. Assuming that the action spectrum for cell inactivation can be approximated by the fluorescence excitation spectrum of the sensitizer -- which is indeed the case for a number of sensitizers in cells in vitro -- we have considered the situation for 5-aminolevulinic acid-induced PpIX in human tissue. All the way down to about 2 mm below the surface light in the Soret band (-410 nm) would give the largest cell inactivation, while at depth exceeding 2 mm, the conventional 635 nm light would be optimal. Light at the argon laser wavelength 514.5 nm is more efficient than light at 635 nm down to 1 mm. From the surface and down to 6 mm, the 635 nm peak of the excitation spectrum of PpIX, as evaluated per photon incident on the skin surface, is redshifted by less than 2 nm. In some cases photosensitizing photoproducts are formed during PCT, such as photoprotoporphyrin during PCT with PpIX. In such cases it may be advantageous to apply a broad-band light source with a spectrum that covers also part of the action spectrum of this photoproduct.
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