Photodynamic Therapy with Topical dL‐aminolevulinic Acid Delays UV Photocarcinogenesis in Hairless Mice

Stender, Ida‐Marie; Bech-Thomsen, Niels; Poulsen, Thomas; Wulf, Hans Christian

doi:10.1111/j.1751-1097.1997.tb03178.x

Cited by 80 publications

(72 citation statements)

References 13 publications

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“…12 It has been shown that PpIX, produced from ALA as well as from ALA-Me, protects against UV-induction of skin tumors in mice. 13,14 PpIX induced by ALA-Me seems to have a shorter lifetime in the tissues than PpIX induced by ALA. 15 This is also clearly manifested in mouse skin after short time (1 hr) topical application of the drugs (Fig. 7, skin measurements) as well as after long time (12 hr, skin measurements) application.…”

Section: Discussionmentioning

confidence: 99%

Pharmacology of protoporphyrin IX in nude mice after application of ALA and ALA esters

Moan¹,

Wei²,

Juzeniene³

et al. 2002

Intl Journal of Cancer

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Aminolevulinic acid (ALA), ALA methylester (ALA-Me) and ALA hexylester (ALA-Hex) were topically applied for 5 and 20 hr, respectively, on normal skin of mice. The distribution of protoporphyrin IX (PpIX) induced in 7 different tissues by these drugs was determined either by spectrofluorometric measurements with an optical fibre probe or by chemical extraction of PpIX from the tissues. The results from these 2 types of measurements were compared. Both methods showed that ALA and the esters induced similar amounts of PpIX at the skin spot where they were applied and that the esters produced much less PpIX at remote skin spots (i.e., spots outside the location where the drugs were applied) than ALA did, notably after 20 hr application. After 20 hr of drug application ALA produced much more PpIX in liver, intestine and lungs than the esters did. In contrast with the direct fluorescence measurements, the extraction method showed detectable amounts of PpIX in liver, intestine and lung after application of the esters, notably of ALAMe. The discrepancy is probably related to the fact that the pigmented tissues absorb light and, therefore, the direct fluorescence readings are misleading. Notably in the liver, which contains high concentration of light-absorbing pigments, very weak direct fluorescence was seen. In no case there was any accumulation of PpIX in muscle tissue nor in brain. The esters seem to penetrate less into the circulation than ALA, and PpIX formed by them in the skin is faster cleared than PpIX formed from ALA. This is also true after oral and i.p. administration of the drugs. © 2002 Wiley-Liss, Inc. Key words: ALA; ALA-esters; pharmacology; PDT; protoporphyrin IXThe use of 5-aminolevulinic acid (ALA) for fluorescence detection (FD) and photodynamic therapy (PDT) of tumors has several advantages over traditional PDT, where photosensitizing dyes are injected intravenously or given orally. First, ALA can be applied topically because ALA molecules are small enough to penetrate the stratum corneum. 1 Second, ALA-induced protoporphyrin IX (PpIX) is cleared from the body more rapidly than other sensitizers, and, therefore, gives less and shorter lasting cutaneous photosensitization.A limitation of ALA-PDT is the shallow penetration of ALA into tissues. ALA-esters, which are more lipophilic than ALA, 2 were introduced to get a deeper penetration and thus facilitate the treatment of larger tumors. [3][4][5] Porphyrins in biological samples, such as cells and skin, are often quantified by direct fluorescence readings. It is well known, however, that these dyes, notably lipophilic ones like PpIX, have a strong tendency to aggregate in aqueous solutions. 6,7 Furthermore, the aggregates have much lower fluorescence quantum yields and photosensitizing efficiencies than monomers. 6 -8 Different degrees of aggregation may take place in different organs. This, in addition to different degrees of pigmentation, makes direct fluorescence measurements of limited value in pharmacological studies where concentration levels i...

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Section: Discussionmentioning

confidence: 99%

Pharmacology of protoporphyrin IX in nude mice after application of ALA and ALA esters

Moan¹,

Wei²,

Juzeniene³

et al. 2002

Intl Journal of Cancer

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“…The lack of appearance of BCCs in the treated areas compared with the rest of the body in both patient 1 and patient 2 suggests that ALA-PDT may inhibit new BCC development, as well as new BFHs in patient 2. Whether this inhibition is due to destruction of subclinical lesions 47,48 or possibly to a local PDT-induced immune response 49 is currently being investigated.…”

Section: Durabilitymentioning

confidence: 99%

Treatment of Diffuse Basal Cell Carcinomas and Basaloid Follicular Hamartomas in Nevoid Basal Cell Carcinoma Syndrome by Wide-Area 5-Aminolevulinic Acid Photodynamic Therapy

Oseroff¹,

Shieh²,

Frawley³

et al. 2005

Arch Dermatol

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“…Topical PDT has only been anecdotally suspected to induce skin tumors such as melanomas [24] or keratoacanthomas [25]. In vitro and in vivo studies did not provide evidence for any carcinogenic effect on skin: both systemic and topical PDT with aminolevulinic acid delayed the occurrence of UV-induced squamous cell carcinoma in mice [26,27]. Preventive repeated MAL-PDTs have a protective effect against UV-induced tumors [28].…”

Section: Discussionmentioning

confidence: 99%

Facial Basal Cell Carcinomas Recurring after Photodynamic Therapy: A Retrospective Analysis of Histological Subtypes

et al. 2012

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Background: Photodynamic therapy (PDT) is an established treatment for basal cell carcinomas (BCCs). Although recurrences are sometime observed, their histological patterns have never been specifically studied or compared with the one of the initial tumor. Objective: To compare the histopathological aggressiveness of BCCs recurring after PDT with that of the primary tumors. Methods: The study population included 12 patients with 16 post PDT recurrent BCCs. Outcome measures were proportion of histologically aggressive subtypes in BCC recurrences vs. primary tumor. Results: 62.5% of recurrent BCCs displayed a transition from a non-aggressive to an aggressive subtype. Conclusions: Post PDT recurrences appear to display an increased histological aggressiveness, although the latter may reflect the natural course of tumor progression. Despite the presence of potential biases, our study raises the possibility that PDT favors the selection of more aggressive tumor cells. Better systematic large-scale follow-up studies are required to assess the exact frequency and histological types of BCC recurrences after PDT.

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Photodynamic Therapy with Topical dL‐aminolevulinic Acid Delays UV Photocarcinogenesis in Hairless Mice

Cited by 80 publications

References 13 publications

Pharmacology of protoporphyrin IX in nude mice after application of ALA and ALA esters

Pharmacology of protoporphyrin IX in nude mice after application of ALA and ALA esters

Treatment of Diffuse Basal Cell Carcinomas and Basaloid Follicular Hamartomas in Nevoid Basal Cell Carcinoma Syndrome by Wide-Area 5-Aminolevulinic Acid Photodynamic Therapy

Facial Basal Cell Carcinomas Recurring after Photodynamic Therapy: A Retrospective Analysis of Histological Subtypes

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