title: Comparison of ALA- and ALA hexyl-ester-induced PpIX depth distribution in human skin carcinoma.
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.
authors.affiliation: Laboratory of Photomedicine, Ecole Polytechnique Fédérale de Lausanne (EPFL), SB, ISIC-GE, Building CH, Station 6, 1015 Lausanne, CH, Switzerland. n.dognitz@pnnmedical.com
authors.forename: Nora
authors.initials: N
authors.lastname: Dögnitz
authors.forename: Denis
authors.initials: D
authors.lastname: Salomon
authors.forename: Matthieu
authors.initials: M
authors.lastname: Zellweger
authors.forename: Jean-Pierre
authors.initials: JP
authors.lastname: Ballini
authors.forename: Tanja
authors.initials: T
authors.lastname: Gabrecht
authors.forename: Norbert
authors.initials: N
authors.lastname: Lange
authors.forename: Hubert
authors.initials: H
authors.lastname: van den Bergh
authors.forename: Georges
authors.initials: G
authors.lastname: Wagnières
mesh_terms: D000287:Administration, Topical; D000622:Aminolevulinic Acid / Q000008:administration & dosage* / Q000031:analogs & derivatives*; D002280:Basal Cell Carcinoma / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D008297:Male; D008856:Microscopy, Fluorescence; D017319:Photosensitizing Agents / Q000008:administration & dosage*; D011524:Protoporphyrins / Q000378:metabolism*; D012878:Skin Neoplasms / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D013050:Spectrometry, Fluorescence; D013997:Time Factors
chemical_list: D017319:Photosensitizing Agents; D011524:Protoporphyrins; D000622:Aminolevulinic Acid; C028025:protoporphyrin IX; C419924:5-aminolevulinic acid hexyl ester