title: Kinetics and localisation of PpIX fluorescence after topical and systemic ALA application, observed in skin and skin tumours of UVB-treated mice.
abstract: In this study the kinetics and localisation of protoporphyrin IX (PpIX) fluorescence in skin and skin tumours were examined after topically (20% for 4h) or systemically (200 mg/kg,i.p.) administered 5-aminolaevulinic acid (ALA). As a model we used hairless mice with skin lesions (actinic keratoses and squamous cell carcinoma), which were induced by daily UVB irradiation. The epidermis of the skin surrounding the tumours (T) was altered (AS); owing to the UVB irradiation, the epidermis was thicker and less elastic. Therefore, non-UVB-irradiated mice were used to assess fluorescence of normal skin (NS). Light from a halogen lamp was used to excite at 500 +/- 20 nm and fluorescence was detected through a filter that passes light of 670 +/- 50 nm. Maximal fluorescence following i.p. ALA was observed 2 h post injection (p.i.) and was three times less than after topically applied ALA. Furthermore, after i.p. ALA a lower T selectively (T/NS) could be obtained than after topically applied ALA. Maximal fluorescence following topically applied ALA was achieved 6 h after the end of the 4 h application time. At that interval fluorescence of T was twice as high as directly after the application period. Furthermore, T selectivity (T/NS) after topical ALA at the interval of maximal fluorescence was higher than at the interval directly after application. With fluorescence cryomicroscopy localisation of fluorescence in the skin at the interval of maximal fluorescence was determined after both administration routes. For both cases fluorescence was mainly located in T, epidermis and hair follicles. Fluorescence in subcutis could only be observed at 2 h post i.p. ALA and a 6 h post topical ALA. No fluorescence could be observed in muscle. We conclude that, in this model and with these ALA doses, a higher fluorescence intensity and selectivity (T/NS) was achieved after topically applied ALA than after systemically administered ALA. These results make topically applied ALA more favourable for ALA-PDT of superficial skin tumours in this model. In general these results imply that by optimising the time after ALA application the efficacy and selectivity of topical ALA-PDT for skin tumours may be improved.
authors.affiliation: Dr Daniel den Hoed Cancer Centre; Department of Clincal Physics, PDT research Laboratory, Rotterdam, The Netherlands.
authors.forename: N
authors.initials: N
authors.lastname: van der Veen
authors.forename: H S
authors.initials: HS
authors.lastname: de Bruijn
authors.forename: R J
authors.initials: RJ
authors.lastname: Berg
authors.forename: W M
authors.initials: WM
authors.lastname: Star
mesh_terms: D000287:Administration, Topical; D000622:Aminolevulinic Acid / Q000008:administration & dosage / Q000378:metabolism / Q000493:pharmacokinetics*; D000818:Animals; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy / Q000378:metabolism*; D005260:Female; D007274:Injections, Intraperitoneal; D007634:Keratitis / Q000378:metabolism; D051379:Mice; D008856:Microscopy, Fluorescence; D010778:Photochemotherapy; D017319:Photosensitizing Agents / Q000378:metabolism*; D011524:Protoporphyrins / Q000096:biosynthesis / Q000378:metabolism*; D012867:Skin / Q000378:metabolism* / Q000528:radiation effects*; D012878:Skin Neoplasms / Q000188:drug therapy / Q000378:metabolism*; D014466:Ultraviolet Rays / Q000009:adverse effects*
chemical_list: D017319:Photosensitizing Agents; D011524:Protoporphyrins; D000622:Aminolevulinic Acid; C028025:protoporphyrin IX