5-aminolaevulinic acid photodynamic therapy in a transgenic mouse model of skin melanoma

Photodynamic therapy (PDT) is widely used to treat preneoplastic skin lesions and non-melanoma skin tumours. Studies analyzing the effects of PDT on malignant melanoma have yielded conflicting results. On the one hand, melanoma cell lines in culture as well as cell lines transplanted into experimental animals were sensitive to PDT. On the other hand, spontaneous melanomas of human patients responded poorly to most PDT regimens tested so far. Here, we analyzed effects of 5-aminolaevulinic acid (5-ALA)-based PDT on melanoma cell lines and on experimental melanomas. To mimic the clinical situation as closely as possible, metallothionein-I/ret (MT-ret) mice, a transgenic model of skin melanoma development, were used. Optimal doses of 5-ALA as well as energy doses and power densities were determined in vitro using a cell line (Mel25) established by us from a melanoma of an MT-ret transgenic mouse as well as commercially available human and mouse melanoma cell lines. Treatment with light irradiation alone had no effect. In combination with 5-ALA, however, this illumination readily induced the death of all mouse and human melanoma cell lines examined. Still, 5-ALA PDT caused only minor focal regressive changes including haemorrhages and fibrosis of MT-ret melanomas in vivo and did not significantly delay tumour growth. These results show that, even though MT-ret melanoma cells are vulnerable to 5-ALA PDT in vitro, malignant MT-ret melanomas in vivo are quite resistant to this type of therapy at doses which are highly effective in vitro.     

Photodynamic therapy of superficial basal cell carcinomas using exogenous 5-aminolevulinic acid and 514-nm light

Objective The evaluation of the effectiveness of topical photodynamic therapy with 5-aminolevulinic acid (5-ALA) and green laser light on superficial basal cell carcinomas. Background Topical photodynamic therapy with exogenous 5-ALA and visible or red laser light has been used up to now for the treatment of superficial non-melanoma skin tumors. Patients and methods Four patients with nine superficial carcinomas participated in this study. The tumors were irradiated with green laser light 5 h after the application of cold cream with 20% aminolevulinic acid under occlusive dressing. Results All nine lesions were resolved with a single treatment and clinical evidence of recurrence was observed in one tumor 1 year after the therapy. Conclusion Topical photodynamic therapy with exogenous 5-ALA and green laser light is very effective for superficial basal cell carcinomas.     

Complete resolution of a squamous cell carcinoma of the skin using intralesional 5-aminolevulinic acid photodynamic therapy intralesional PDT for SCC

We present an 82-year-old female patient with a 2-year history of an infiltrative squamous cell carcinoma (SCC) on her right cheek. The patient was treated with one intralesional photodynamic therapy (PDT) session using 10% 5-aminolevulinic acid solution. We used red light by a non-coherent light source at a light dose of 100 J/cm2 and a fluency rate of 100 mW/cm2. Complete clinical and histological response was achieved 3 months after the treatment procedure. Cosmetic outcome was evaluated as fair. The patient remains disease free with the absence of any clinical sign of recurrence 16 months after PDT. Long-term follow-up is needed for assessment of recurrences. Optimization of the therapeutic protocol, as well as justification of our results in larger studies are needed in order to elicit safe conclusions.     

Evidence for a bystander role of neutrophils in the response to systemic 5-aminolevulinic acid-based photodynamic therapy

BACKGROUND/PURPOSE: A significant increase in the number of circulating and tumour neutrophils immediately after therapy was observed while investigating the increase in response of tissues to aminolevulinic acid-based photodynamic therapy (ALA-PDT) using a twofold illumination scheme with a prolonged dark interval. The action of (tumour) neutrophils is an important therapeutic adjunct to the deposition of singlet oxygen within the treatment volume, for many photosensitizers. It is not known if those phagocytes contribute to the improved outcome of ALA-PDT. In this study we investigated the role of neutrophils in the response to PDT using systemic ALA with and without light fractionation. METHODS: Rhabdomyosarcoma, transplanted in the thigh of female WAG/Rij rats were illuminated transdermally using 633 nm light following i.v. administration of 200 mg/kg ALA. The pharmacokinetics of protoporphyrin IX (PpIX) within the tumour tissue during therapy were determined to compare with that observed in other models for topical administration of ALA. PDT was performed under immunologically normal or neutropenic conditions using various illumination schemes. The number of neutrophils in tumour and in the circulation were determined as a function of time after treatment and compared with growth delay of each scheme. RESULTS: Fluorescence spectroscopy revealed similar pharmacokinetics of PpIX to those observed during and after topical ALA-PDT. The number of neutrophils within the illuminated tumour and in the circulation increased significantly following therapy. This increase in the number of neutrophils was associated with an increase in the efficacy of therapy: the more effective the therapy the greater the increase in tumour and blood neutrophils. Administration of anti-granulocyte serum treatment prevented the influx of neutrophils after ALA-PDT, but did not lead to a significant decrease in the efficacy of the PDT treatment on the growth of the tumour for any illumination scheme investigated. CONCLUSION: These results indicate that the magnitude of damage inflicted on the tumour by ALA-PDT does not depend on the presence of neutrophils in the tumour or circulation and that the role of neutrophils in ALA-PDT is much less important than in PDT using other photosensitizers. These data contribute to the understanding of the mechanism of response of tissue to systemic ALA-PDT.     

Topical photodynamic therapy with 5-aminolevulinic acid in Chinese patients with Rosacea

Background: Rosacea is difficult to cure and frequently recurs. Topical photodynamic therapy (PDT) has been tentatively used, with only preliminary results reported.

Objective: To evaluate the efficacy and safety of topical PDT in Chinese patients with rosacea.

Methods & Materials: Seventeen participants with rosacea were treated three times using 5-aminolevulinic acid (ALA)-PDT at intervals of 7–10 days. Papule and pustule numbers, erythema severity, telangiectasia severity, physician’s global assessment (PGA) score (1 [best]–6), and patient satisfaction score (0–3 [highest]) were assessed. Rosacea improvement and the total effective rate were calculated. Stratum corneum hydration and sebum levels, and the melanin index (MI) and erythema index (EI) were measured non-invasively.

Results: After three treatments with ALA-PDT, the total effective rate (≥50% improvement) was 64.71%, mean PGA score was 2.88 ± 0.93, and mean patient satisfaction score was 1.71 ± 0.69. The EI significantly decreased 1 month after the final treatment (from 468 ± 80.61 to 439 ± 77.78 for the forehead and from 507.65 ± 92.51 to 483.27 ± 78.32 for the nasal ala). Four participants received three additional treatments. They achieved 50–74% improvement after three treatments and ≥75% improvement after six treatments.

Conclusion: ALA-PDT is safe and effective for treating rosacea.     

Influence of topical photodynamic therapy with 5-aminolevulinic acid on porphyrin metabolism

Photodynamic therapy (PDT) with topically applied 5-aminolaevulinic acid (5-ALA) is increasingly used for treating tumours. The efficacy of topical PDT is limited to superficial and initial tumours. The topically applied doses of 5-ALA vary from 0.02 to 7.0 g per session according to the type of lesion. There are no studies on the influence of topically applied 5-ALA on the systemic accumulation of porphyrins or porphyrin precursors. A group of 20 patients with actinic keratoses (AK) and basal cell carcinomas (BCC) were treated by topical PDT with 5-ALA. Prior to and 6 and 24 h after PDT, 5-ALA and total porphyrin concentrations were determined in red blood cells and plasma, respectively. In addition, before and after 5-ALA treatment, 24-h urine samples were collected and porphyrins and porphyrin precursors were measured. There was no significant alteration in porphyrin metabolism. In some patients, a slight but insignificant increase in erythrocyte and plasma porphyrins was found 6 h after 5-ALA PDT. This investigation confirms clearly the safety of this treatment modality and demonstrates that 5-ALA application (up to 7 g) in the course of PDT has no influence on the concentrations of porphyrins and porphyrin precursors measured in various compartments.     

Pain associated with photodynamic therapy using 5-aminolevulinic acid or 5-aminolevulinic acid methylester on tape-stripped normal skin

BACKGROUND: Pain during and after topical photodynamic therapy (PDT) is one of the few severe adverse effects of the new treatment of skin diseases. OBJECTIVE: To compare the pain experienced in normal skin treated with 5-aminolevulinic acid (ALA) PDT and 5-aminolevulinic methylester (ALA-ME) PDT. DESIGN: Double-blind randomized trial. INTERVENTIONS: Twenty healthy volunteers were treated randomly with ALA-PDT on one forearm and ALA-ME-PDT on the other forearm after tape stripping of the sun-exposed skin areas. MAIN OUTCOME MEASURES: Pain was scored using a numerical scale ranging from 0 to 10 during illumination, immediately after illumination, and each day in the following week. In addition, we measured erythema, pigmentation, and protoporphyrin IX (PpIX) fluorescence. RESULTS: ALA-PDT generated significantly more pain than ALA-ME-PDT during and after illumination (P =.001 and P =.05, respectively). ALA-PDT induced a larger decrease in PpIX fluorescence than ALA-ME-PDT (P =.009). There was no correlation between pain and peak PpIX fluorescence or absolute decrease in peak PpIX fluorescence. Both treatments lead to erythema immediately after illumination and increased pigmentation 1 week after PDT. There was no correlation between pain and degree of erythema or pigmentation. CONCLUSIONS: ALA-ME-PDT was less painful than ALA-PDT when performed on tape-stripped normal skin. The pain scores did not correlate with the intensity of peak PpIX fluorescence in the skin or with the degree of erythema after illumination, suggesting that pain was not caused by activation of PpIX alone. The theory that ALA and not ALA-ME is transported by gamma-aminobutyric acid receptors into the peripheral nerve endings may explain the higher pain scores in ALA-PDT-treated areas.     

Successful treatment of cutaneous leishmaniasis with intralesional aminolevulinic acid photodynamic therapy

Leishmaniasis is a protozoan infectious disease that often affects the skin and may acquire a chronic and difficult to treat course. Topical photodynamic therapy (PDT) is a novel treatment which involves the selective uptake of a photosensitizing agent. Exposure to an appropriate light source in the presence of oxygen leads to formation of reactive oxygen species and destruction of the target cells. We report on the successful treatment of a 69-year-old patient with a relapse of long-standing cutaneous leishmaniasis using intralesional aminolevulinic acid-PDT.     

5-氨基酮戊酸光动力疗法治疗HPV感染相关宫颈肿瘤的研究进展

 宫颈癌是全球女性第四高发和死亡的恶性肿瘤,是女性健康的严重威胁之一,主要由人乳头瘤病毒(HPV)感染引起。5-氨基酮戊酸光动力疗法（ALA-PDT）通过光敏剂的激活产生一系列光生化反应杀伤肿瘤细胞,因其在特异选择性、组织创伤性、安全重复性等方面的优势,已在临床上广泛应用于多种疾病包括宫颈肿瘤中。本文就国内外ALA-PDT治疗HPV感染相关宫颈肿瘤的作用机制和临床应用进展作一综述,旨在为相关机制的深入研究及临床应用提供参考。     

5-氨基酮戊酸光动力学疗法在皮肤科的应用进展

探讨5-氨基酮戊酸（ALA）光动力学疗法（PDT）治疗皮肤病的作用原理及应用范围,为临床合理使用ALA—PDT提供参考依据。对近lO余年来文献报道的有关PDT研究进展及其临床应用的文献进行总结和分析,综述ALA．PDT治疗各类皮肤病的作用原理和机制,以及ALA．PDT治疗皮肤病的范围,所引起的不良反应。PDT对皮肤肿瘤、红斑鳞屑性皮肤病、人乳头瘤病毒（HPV）感染性皮肤病、痤疮、鲜红斑痣等均有良好的临床效果,不良反应相对较小,在皮肤科有很大的应用前景。     

Photodynamic therapy using direct-current pulsed iontophoresis for 5-aminolevulinic acid application

In photodynamic therapy (PDT) for skin cancer, 5-aminolevulinic acid (ALA) is applied topically to the affected area to be absorbed percutaneously through passive diffusion, and typically requires 4–6 h before performing PDT. In this study, we attempted to reduce the absorption period in PDT by ionizing ALA using direct-current pulsed iontophoresis to treat actinic keratosis (AK). Twenty percent ALA solution was applied to AK lesions of five patients using direct-current pulsed iontophoresis. ALA-PDT was repeated three times with a total irradiation of 150 J/cm² (50 J/cm² per irradiation, weekly). One week after the last PDT, therapeutic results were assessed by skin biopsy. In all subjects, protoporphyrin IX (PpIX) production was confirmed after iontophoresis, and its production levels were comparable to the conventional occlusive dressing technique (ODT). Skin biopsies from the treated lesion showed the disappearance of tumour cells. These results indicated that direct-current pulsed iontophoresis for applying ALA before PDT is useful to treat AK.     

5-氨基酮戊酸光动力疗法治疗宫颈尖锐湿疣临床研究

目的 探讨5-氨基酮戊酸光动力疗法（ALA-PDT）治疗宫颈尖锐湿疣患者的疗效和安全性。方法 治疗组采用ALA-PDT对45例宫颈尖锐湿疣患者进行治疗,每2周治疗1 次,治疗1 ~ 4次后判断临床疗效。对照组采用CO2激光对35例宫颈尖锐湿疣患者进行治疗,两组随访时间均为3个月。结果 治疗组45例患者中,3例经1次ALA-PDT治疗、6例2次治疗、20例3次治疗、15例4次治疗获得完全缓解,完全缓解率为97.8%（44/45）;复发3例,复发率6.8%（3/44）。对照组30例患者一次性去除疣体,5例分批治疗,完全缓解率为100％（35/35）,复发率为31.4％（11/35）。经统计学处理,两组间完全缓解率,差异无统计学意义（P > 0.05）,复发率对照组明显高于治疗组（χ2 = 6.497,P < 0.05）。治疗组几乎所有患者在红光照射期间出现轻度下腹部坠胀感,但未发现明显不良反应和瘢痕形成。对照组不良反应主要表现为出血、糜烂、浅溃疡和瘢痕。结论 ALA-PDT具有疗效好、副作用小、复发率低等优势,可作为治疗宫颈尖锐湿疣的治疗选择之一。     

5-氨基酮戊酸光动力疗法治疗光老化

长期紫外线辐射形成的光老化不仅有碍容颜,也存在发生皮肤肿瘤的风险,有必要采取相应治疗.5-氨基酮戊酸联合红光、蓝光、强脉冲光和脉冲染料激光等光源的光动力疗法近年来在治疗光老化及光损伤相关皮肤问题上疗效肯定,获得明显美容效果.氨基酮戊酸-光动力疗法作为非创伤性嫩肤技术新成员,显示出一定的应用前景.     

5-氨基酮戊酸光动力疗法治疗面部扁平疣疗效评价

目的：评价5-氨基酮戊酸光动力（5-ALA—PDT）治疗面部扁平疣的疗效。方法：面部扁平疣患者48例,治疗组24例,采用5-氨基酮戊酸光动力疗法每周1次。对照组24例,用波长532nm的Q开关Nd：YAG激光照射皮损每周1次。疗程均为3周。治疗结束后判定两组疗效。末次观察后3个月判定两组复发率。结果：治疗组痊愈率为91．67％。3个月后随访,复发l例,复发率为4．17％;对照组痊愈率为83．33％,复发5例,复发率为20．83％,两组复发率有显著性差异（P〈0．05）。结论：5-ALA—PDT治疗扁平疣有效、复发率低。     

Incomplete efficacy of 5-aminolevulinic acid (5 ALA) photodynamic therapy in the treatment of widespread extramammary Paget's disease

Photodynamic therapy (PDT) using 5-aminolevulinic acid (5-ALA) is an effective treatment for several conditions such as Bowen's disease, subsets of basal cell carcinomas and actinic keratosis. Surgical resection is the first-choice therapy for extramammary Paget's disease (EMPD), but extensive resection is highly invasive and recurrences are frequent. We report two cases of genital EMPD treated by PDT with partial efficacy. The first patient, a 78-year-old male, suffered from pubic and scrotal Paget's disease for 6 years despite numerous treatments. The second patient, a 78-year-old female, had vulvar involvement for 2 years that was resistant to multiple treatments. The disease was recurrent and chronic with important pruritus and significant impact on the quality of life. Methyl 5-aminolevulinate was applied for 3 h, and irradiation was applied with red light (630 nm) using a total light dose of 37 J/cm(2) for a period of 10 min. The patients were treated every 2 to 4 weeks for a total of at least three treatments. Both patients experienced a partial transient reduction in their symptoms. One patient had a partial transient remission (< 50% reduction of the involved surface), whereas in the other patient, PDT failed to reduce the surface area of the lesions.     

Photodynamic therapy using a novel irradiation source,LED lamp,is similarly effective to photodynamic therapy using diode laser or metal‐halide lamp on DMBA‐ and TPA‐induced mouse skin papillomas

Photodynamic therapy (PDT) is useful for superficial skin tumors such as actinic keratosis and Bowen disease. Although PDT is non‐surgical and easily‐performed treatment modality, irradiation apparatus is large and expensive. Using 7, 12‐dimethylbenz[a]anthracene (DMBA) and 12‐ο‐tetradecanoylphorbol‐13‐acetate (TPA)‐induced mouse skin papilloma model, we compared the efficacy of TONS501‐ and ALA‐PDT with a LED lamp, a diode laser lamp or a metal‐halide lamp on the skin tumor regression. TONS501‐PDT using 660 nm LED lamp showed anti‐tumor effect at 1 day following the irradiation and the maximal anti‐tumor effect was observed at 3 days following the irradiation. There was no significant difference in the anti‐tumor effects among TONS501‐PDT using LED, TONS501‐PDT using diode laser, and 5‐aminolevulinic acid hydrochloride (ALA)‐PDT using metal‐halide lamp. Potent anti‐tumor effect on DMBA‐ and TPA‐induced mouse skin papilloma was observed by TONS501‐PDT using 660 nm LED, which might be more useful for clinical applications.