A time course investigation of the fluorescence induced by topical application of 5‐aminolevulinic acid and methyl aminolevulinate on normal human skin

Lesar, Andrea; Ferguson, J.; Moseley, Harry

doi:10.1111/j.1600-0781.2009.00436.x

Cited by 18 publications

(11 citation statements)

References 27 publications

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“…ALA and MAL produce the same intracellular photosensitizer (PpIX), penetrate human skin to similar depths and produce a similar spatial distribution of PpIX in murine skin . However, ALA produces relatively greater amounts of PpIX (Juzeniene et al, 2006) and higher levels of fluorescence with a slower time course than MAL in human skin (Lesar et al, 2009). This, together with greater local edema reported after ALA compared with MAL-PDT in mice and the possibility of different microscopic PpIX distributions following ALA and MAL application to human skin, could explain the greater immunosuppression observed after ALA-PDT in our study.…”

Section: Discussionmentioning

confidence: 73%

Photodynamic Therapy–Induced Immunosuppression in Humans Is Prevented by Reducing the Rate of Light Delivery

Frost

Halliday

Damian

2011

Journal of Investigative Dermatology

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Photodynamic therapy (PDT) of non-melanoma skin cancers currently carries failure rates of 10-40%. The optimal irradiation protocol is as yet unclear. Previous studies showed profound immunosuppression after PDT, which may compromise immune-mediated clearance of these antigenic tumors. Slower irradiation prevents immunosuppression in mice, and may be at least as effective as high-fluence-rate PDT in preliminary clinical trials. The photosensitizers 5-aminolaevulinic acid and/or methyl aminolaevulinate were applied to discrete areas on the backs of healthy Mantoux-positive volunteers, followed by narrowband red light irradiation (632 nm) at varied doses and fluence rates. Delayed type hypersensitivity (Mantoux) reactions were elicited at test sites and control sites to determine immunosuppression. Human ex vivo skin received low- and high-fluence-rate PDT and was stained for oxidative DNA photolesions. PDT caused significant, dose-responsive immunosuppression at high (75 mW cm(-2)) but not low (15 or 45 mW cm(-2)) fluence rates. DNA photolesions, which may be a trigger for immunosuppression, were observed after high-fluence-rate PDT but not when light was delivered more slowly. This study demonstrates that the current clinical PDT protocol (75 mW cm(-2)) is highly immunosuppressive. Simply reducing the rate of irradiation, while maintaining the same light dose, prevented immunosuppression and genetic damage and may have the potential to improve skin cancer outcomes.

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Section: Discussionmentioning

confidence: 73%

Photodynamic Therapy–Induced Immunosuppression in Humans Is Prevented by Reducing the Rate of Light Delivery

Frost

Halliday

Damian

2011

Journal of Investigative Dermatology

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“…In a previous study, the total porphyrin levels in basal cell carcinoma and squamous cell carcinoma showed maximum values of 2 to 6 hours32. In addition, the effect of PpIX fluorescence after the application of ALA is dependent on the duration of the application33. Therefore, we performed 5-ALA treatment for 6 hours to achieve high complete response rates.…”

Section: Discussionmentioning

confidence: 94%

“…Until now, the time point for maximum porphyrin accumulation because of 5-ALA application is still controversial for AKs32,33. In many clinical studies, the application time of 5-ALA was 3 to 6 hours11,13,18,19,20,23.…”

Section: Discussionmentioning

confidence: 99%

Comparative Study of Photodynamic Therapy with Topical Methyl Aminolevulinate versus 5-Aminolevulinic Acid for Facial Actinic Keratosis with Long-Term Follow-Up

Kim

Song

2014

Ann Dermatol

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BackgroundFew studies have compared the efficacy, cosmetic outcomes, and adverse events between 5-aminolevulinic acid photodynamic therapy (ALA-PDT) and methyl aminolevulinate-PDT (MAL-PDT) for actinic keratoses (AKs) in Asian ethnic populations with dark-skin.ObjectiveWe retrospectively compared the long-term efficacy, recurrence rates, cosmetic outcomes, and safety of ALA-PDT versus MAL-PDT for facial AKs in Koreans.MethodsA total of 222 facial AKs in 58 patients were included in this study. A total of 153 lesions (29 patients) were treated with 5-ALA, and 69 lesions (29 patients) with MAL. ALA and MAL creams were applied for 6 hours and 3 hours, respectively; the lesions were then illuminated with a halogen lamp at 150 J/cm2 for ALA-PDT and a diode lamp at 37 J/cm2 for MAL-PDT.ResultsThe complete response rates of ALA-PDT and MAL-PDT were 56.9% and 50.7%, respectively, with no significant difference at 12 months after treatment. No significant difference in recurrence rates was observed between the 2 PDT modalities at either 6 or 12 months after treatment. There was no significant difference in the cosmetic outcomes between the 2 treatment modalities at 12 months after PDT. However, ALA-PDT caused significantly more painful than MAL-PDT (p=0.005). The adverse events were mild to moderate, transient, and self-limiting for both modalities.ConclusionMAL-PDT was similar to ALA-PDT in terms of long-term efficacy, recurrence rates, cosmetic outcomes, and adverse events; however, it was a significantly less painful procedure than ALA-PDT in our study.

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“…ALA-and MAL-induced fluorescence has been examined in normal, healthy, human skin [26,31]. Fluorescence intensities from 20% ALA and MAL compounds depended on the duration of application and ALA gave higher PpIX surface fluorescence on intact skin than what was found for MAL after for 1-6 hours of application [31] and after long-term application up to 24 hours [26]. The present study shows that a short incubation time of 30 minutes on intact skin with MAL induces higher PpIX fluorescence intensities than with ALA, which has not been previously reported.…”

Section: Discussionmentioning

confidence: 99%

Pretreatment with ablative fractional laser changes kinetics and biodistribution of topical 5‐aminolevulinic acid (ALA) and methyl aminolevulinate (MAL)

et al. 2014

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Background and Objectives: 5-Aminolevulinic acid (ALA) and methyl aminolevulinate (MAL) are porphyrin precursors used topically for photodynamic therapy (PDT). Previous studies have established that ablative fractional laser (AFXL) increases topical drug uptake. We evaluated kinetics and biodistribution of ALA-and MAL-induced porphyrins on intact and disrupted skin due to AFXL. Materials and Methods: Two Yorkshire swine were exposed to CO 2 AFXL (10.6 mm, 1,850 mm ablation depth) and subsequent topical application of ALA and MAL cream formulations (20%, weight/weight). Porphyrin fluorescence was quantified by digital fluorescence photography (30, 90, and 180 minutes) and fluorescence microscopy at specific skin depths (180 minutes). Results: Porphyrins gradually formed over time, differently on intact and AFXL-disrupted skin. On intact skin (no AFXL), fluorescence photography showed that MAL initially induced higher fluorescence than ALA (t ¼ 30 minutes MAL 21.1 vs. ALA 7.7 au, t ¼ 90 minutes MAL 39.0 vs. ALA 26.6 (P < 0.009)) but reached similar intensities for long-term applications (t ¼ 180 minutes MAL 56.6 vs. ALA 52 au, P ¼ ns). AFXL considerably enhanced porphyrin fluorescence from both photosensitizers (P < 0.05). On AFXL-exposed skin, MAL expressed higher fluorescence than ALA for short-term application (t ¼ 30 minutes, AFXL-MAL 26.4 vs. AFXL-ALA 14.1 au, P < 0.001), whereas ALA over time overcame MAL and induced the highest fluorescence intensities obtained (t ¼ 180 minutes, AFXL-MAL 98.6 vs. AFXL-ALA 112.0 au, P < 0.001). In deep skin layers, fluorescence microscopy showed higher fluorescence in hair follicle epithelium for ALA than MAL (t ¼ 180 minutes, 1.8 mm, AFXL-MAL 35.3 vs. AFXL-ALA 46.7 au, P < 0.05). Conclusions: AFXL changes kinetics and biodistribution of ALA and MAL. It appears that AFXL-ALA favors targeting deep structures.

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A time course investigation of the fluorescence induced by topical application of 5‐aminolevulinic acid and methyl aminolevulinate on normal human skin

Cited by 18 publications

References 27 publications

Photodynamic Therapy–Induced Immunosuppression in Humans Is Prevented by Reducing the Rate of Light Delivery

Photodynamic Therapy–Induced Immunosuppression in Humans Is Prevented by Reducing the Rate of Light Delivery

Comparative Study of Photodynamic Therapy with Topical Methyl Aminolevulinate versus 5-Aminolevulinic Acid for Facial Actinic Keratosis with Long-Term Follow-Up

Pretreatment with ablative fractional laser changes kinetics and biodistribution of topical 5‐aminolevulinic acid (ALA) and methyl aminolevulinate (MAL)

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