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Comparison of ALA- and ALA hexyl-ester-induced PpIX depth distribution in human skin carcinoma

Dögnitz, Nora
Zellweger, Matthieu
Ballini, Jean-Pierre
Gabrecht, Tanja
van den Bergh, Hubert
Wagnières, Georges
Published in Journal of Photochemistry and Photobiology. B, Biology. 2008, vol. 93, no. 3, p. 140-8
Abstract Photodynamic therapy (PDT) based on the use of photoactivable porphyrins, such as protoporphyrin IX (PpIX), induced by the topical application of amino-levulinic acid (ALA) or its derivatives, ALA methyl-ester (m-ALA), is a treatment for superficial basal cell carcinoma (BCC), with complete response rates of over 80%. However, in the case of deep, nodular-ulcerative lesions, the complete response rates are lower, possibly related to a lower bioavailability of PpIX. Previous in vitro skin permeation studies demonstrated an increased penetration of amino-levulinic acid hexyl-ester (h-ALA) over ALA. In this study, we tested the validity of this approach in vivo on human BCCs. An emulsion containing 20% ALA (w/w) and preparations of h-ALA at different concentrations were applied topically to the normal skin of Caucasian volunteers to compare the PpIX fluorescence intensities with an optical fiber-based spectrofluorometer. In addition, the PpIX depth distribution and fluorescence intensity in 26 BCCs were investigated by fluorescence microscopy following topical application of 20% ALA and 1% h-ALA. We found that, for application times up to 24h, h-ALA is identical to ALA as a PpIX precursor with respect to PpIX fluorescence intensity, depth of penetration, and distribution in basal cell carcinoma, but has the added advantage that much smaller h-ALA concentrations can be used (up to a factor 13). We observed a non-homogenous distribution in BCCs with both precursors, independent of the histological type and depth of invasion in the dermis.
Keywords Administration, TopicalAminolevulinic Acid/administration & dosage/analogs & derivativesCarcinoma, Basal Cell/drug therapy/metabolism/pathologyDose-Response Relationship, DrugFemaleHumansMaleMicroscopy, FluorescencePhotosensitizing Agents/administration & dosageProtoporphyrins/metabolismSkin Neoplasms/drug therapy/metabolism/pathologySpectrometry, FluorescenceTime Factors
PMID: 18818091
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DÖGNITZ, Nora et al. Comparison of ALA- and ALA hexyl-ester-induced PpIX depth distribution in human skin carcinoma. In: Journal of Photochemistry and Photobiology. B, Biology, 2008, vol. 93, n° 3, p. 140-8.

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Deposited on : 2009-11-23

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