Photodiagnosis and Photodynamic Therapy

Editorial Board

2012-06-01

Preliminary clinical report on safety and efficacy of photodynamic therapy using talaporfin sodium for malignant gliomas

Jiro Akimoto, Jo Haraoka, Katsuo Aizawa — 2012-03-01

Summary: Objectives: To investigate the safety and efficacy of photodynamic therapy (PDT) using talaporfin sodium in patients with surgically, completely unresectable malignant gliomas with invasion into the eloquent areas of the brain associated with language and motor functions.Materials and methods: Subjects consisted of consecutive 14 adult patients with malignant gliomas that were shown on preoperative diagnostic imaging to have invaded the eloquent areas of the brain. Of these, 6 patients had newly diagnosed tumors and 8 patients had recurrent tumors. In 15 craniotomy and tumor resection procedures, PDT was used as additional intraoperative treatment 24h after 40mg/m2 of talaporfin sodium had been injected intravenously. After the tumor bulk had been resected as extensively as possible either 1 or 2 sites of probable tumor invasion in the bottom of resection cavity were irradiated superficially with a 664-nm diode laser for 180s (27J/cm2) at a power density of 150mW/cm2.Results: PDT achieved a response rate of 80% at the treated sites in the 6 patients with newly diagnosed malignant gliomas. In these patients, the median progression-free survival time was 23 months. The median survival time in 3 patients who died was 26 months, and the remaining 3 patients survived for more than 3 years with a good Karnofsky Performance Scale (KPS). In the 8 patients with recurrent tumors who received PDT, their response rate was low (25.0%), their gliomas recurred 3 months after PDT, and their survival time was only 9 months following PDT. No adverse events directly attributable to PDT occurred in any patients. Protection against light was only required for approximately 3 days after PDT.Conclusion: We examined the safety and efficacy of PDT using talaporfin sodium as an additional intraoperative treatment for malignant glioma. PDT in addition to surgical resection achieved better therapeutic results than conventional protocols, especially in patients with newly diagnosed malignant gliomas. However, the current methodology has some limitations with respect to patients with recurrent tumors. Larger-scale studies are required to confirm the clinical feasibility of PDT plus surgery.

Combination of Fospeg-IPDT and a natural antioxidant compound prevents photosensitivity in a murine prostate cancer tumour model

2011-12-15

Summary: Background: The aim of the present research was to investigate the potential use of a natural compound rich in antioxidant agents, derived from Pinus halepensis (P. halepensis), to prevent PDT induced photosensitivity. The present research progressed in two levels. The first one evolved the optimization of Fospeg-interstitial photodynamic therapy (IPDT) in a prostate cancer animal model. In the second one, P. halepensis bark extract, was evaluated for its potential use to prevent photosensitivity.Methods: Two sets of experiments were performed, IPDT only and IPDT in the presence of antioxidant. For both of them, Fospeg was administrated intravenously to SCID mice bearing prostate cancer, followed by IPDT after 6h. For the IPDT+antioxidant experiments, P. halepensis was injected intratumourously 1h prior the tumour illumination. Treatment outcome was monitored twice a week by an imaging system and by measuring tumour dimensions using a caliper. Photosensitivity was assessed by monitoring erythema of the tail using the imaging system.Results: IPDT with Fospeg and 15J total light energy is a therapeutic scheme that can eliminate tumours in the murine model of prostate cancer. Two months after complete tumour remission no tumour recurrence was observed. Also, the cosmetic outcome of the research was excellent. The major drawback of this treatment scheme was that 90% of the animals developed photosensitivity. The addition of P. halepensis bark extract resulted in prevention of the photosensitivity, leaving PDT outcome unaffected.Conclusions: The combined use of PDT and the used antioxidant agent could broaden the implementation of photodynamic therapy, by eliminating photosensitivity.

Vascular targeted photodynamic therapy for bleeding gastrointestinal mucosal vascular lesions: A preliminary study

Haixia Qiu, Yongping Mao, Ying Gu, Ying Wang, Jianguo Zhu, Jing Zeng — 2011-12-19

Summary: Background: Vascular-targeted photodynamic therapy (V-PDT) has shown good selectivity and efficacy in the treatment of certain types of vascular disease, including port wine stains, age-related macular degeneration, and esophageal varices. This study was conducted to test the efficacy and safety of V-PDT in the treatment of gastrointestinal (GI) bleeding caused by the abnormal dilatation of capillaries.Methods: Patients with bleeding GI mucosal vascular lesions treated with V-PDT were included in this retrospective study. The efficiency of V-PDT was analyzed by comparing the documented endoscopy results, hemoglobin levels, and transfusion requirements before and at 6 months after the last V-PDT. Side effects during and after V-PDT and follow-up results were also analyzed.Results: Seven patients with bleeding GI mucosal vascular lesions were treated with V-PDT. After 1–4 V-PDT sessions, all patients no longer needed transfusions to maintain a stable hemoglobin level during the follow-up period of 6 months. The mean hemoglobin level of the seven patients improved from 6.21±1.48g/dl to 11.66±1.21g/dl (p<0.001), and the GI bleeding and melena of all the patients disappeared. No perforations, strictures, scars, or episodes of photosensitization occurred in the seven patients, and there were no recurrences of GI bleeding during the 1–21 months of further follow-up.Conclusions: This preliminary study indicated that V-PDT is a highly selective, safe, well-tolerated, and effective treatment modality for bleeding GI mucosal vascular lesions. However, prospective studies with larger sample sizes are needed to confirm this finding.

Local clinical phototreatment of herpes infection in São Paulo

Joao Paulo Tardivo, Mark Wainwright, Mauricio S. Baptista — 2012-02-10

Summary: The clinical use of topical photodynamic therapy in herpes simplex lesions in São Paulo is presented and discussed. Although previous attempts utilising this type of approach in the USA were discontinued in the early 1970s due to several presentations of post-treatment Bowen's disease, none of the cases from the clinic presented here have displayed any complications on follow-up. In addition, lesion recrudescence periods are generally much longer than with conventional approaches. This is thought to be due to improvements in the treatment protocol, viz. use of the non-toxic photosensitisers methylene blue and Hypericum perforatum extract in place of proflavine and neutral red in the original trials, differences in photosensitisation pathway and illumination of the treatment site with red rather than fluorescent/UV light. Post-treatment cosmesis is also excellent.

Antibacterial photodynamic therapy for dental caries: Evaluation of the photosensitizers used and light source properties

2011-12-26

Summary: Photodynamic therapy studies have shown promising results for inactivation of microorganisms related to dental caries. A large number of studies have used a variety of protocols, but few studies have analyzed photosensitizers and light source properties to obtain the best PDT dose response for dental caries. This study aims to discuss the photosensitizers and light source properties employed in PDT studies of dental caries. Three questions were formulated to discuss these aspects. The first involves the photosensitizer properties and their performance against Gram positive and Gram negative bacteria. The second discusses the use of light sources in accordance with the dye maximum absorbance to obtain optimal results. The third looks at the relevance of photosensitizer concentration, the possible formation of self-aggregates, and light source effectiveness. This review demonstrated that some groups of photosensitizers may be more effective against either Gram positive or negative bacteria, that the light source must be appropriate for dye maximum absorbance, and that some photosensitizers may have their absorbance modified with their concentration. For the best results of PDT against the main cariogenic bacteria (Streptococcus mutans), a variety of aspects should be taken into account, and among the analyzed photosensitizer, erythrosin seems to be the most appropriate since it acts against this Gram positive bacteria, has a hydrophilic tendency and even at low concentrations may have photodynamic effects. Considering erythrosin, the most appropriate light source should have a maximum emission intensity at a wavelength close to 530nm, which may be achieved with low cost LEDs.

Elastic scattering spectroscopy in assessing skin lesions: An “in vivo” study

2011-12-29

Summary: Introduction: Elastic scattering spectroscopy (ESS) has been shown to be accurate in the identification of abnormalities of soft tissue. These include ischemia and inflammation, pre-cancer and cancer. The aim of this study was to compare findings of ESS with gold standard histopathology in patients with various skin lesions.Materials and methods: Seventy-three patients with clinically suspicious facial skin lesions were included. Those lesions with the surrounding innocuous skin were interrogated by ESS, biopsies were taken and examined histopathologically; the results were then compared.Results: The preliminary analysis showed obvious spectral differences between normal and pathological skin. Spectral differences were identified when comparing benign skin conditions to malignant ones. Spectral differences were identified between basal cell carcinomas and other skin lesions.Conclusions: This preliminary study shows that ESS can distinguish between normal, benign and malignant skin conditions.

The palliative role of PDT in recurrent advanced nasopharyngeal carcinoma: Case series

Syedda Abbas, Waseem Jerjes, Tahwinder Upile, Francis Vaz, Colin Hopper — 2012-03-29

Summary: We report on the application of photodynamic therapy in the management of recurrent advanced carcinoma of the nasopharynx. A selected cohort of 7 patients, only suitable for palliative therapy, was offered this modality to assess the palliative role of PDT. All 7 patients had at least 2 previous recurrences, which were managed with surgery and chemoradiotherapy but ultimately failed to respond.PDT was offered after careful discussion at a multidiscipline meeting. The photosensitiser “mTHPC” was introduced intravenously 96h prior to delivering the light with nasoendoscopic guidance.Six patients’ symptoms were reduced markedly post photodynamic therapy. Five patients have to had another round of treatment which was found to be as effective as the first round in terms of controlling disease progression as well as symptoms.Magnetic resonance images showed variable reduction of tumour volume with the majority of the patients having moderate to significant response.Photodynamic therapy was very successful palliative therapy for this small group of recurrent advanced nasopharyngeal cancer patients.

Comparison of cryotherapy and photodynamic therapy in treatment of oral leukoplakia

2012-01-16

Summary: Oral leukoplakia is a pre-malignant lesion of the oral mucosa. The aim of this study is to compare the curative effects of photodynamic therapy and cryotherapy in the treatment of oral leukoplakia. The first group, treated by photodynamic therapy (δ-aminolevulinic acid (ALA), 630–635nm wavelength), consisted of 48 patients suffering from leukoplakia. The second group consisted of 37 patients treated using cryotherapy. Analyses and comparisons of the complete responses, recurrences, numbers of procedures and adverse effects after both PDT and cryotherapy were obtained. In the first group, a complete response was obtained in 35 patients (72.9%), with thirteen recurrences observed (27.1%) over a six-month period. In the second group, a complete response was obtained in 33 patients (89.2%), and recurrence was observed in nine patients (24.3%). Photodynamic therapy and cryotherapy appear to be comparative methods of treatment that may both serve as alternatives for the traditional surgical treatment of oral leukoplakia. The advantages of PDT are connected with minimally invasive and localized character of the treatment and with not damage of collagenous tissue structures, therefore normal cells will repopulate these arrangements. PDT is more convenient for patients, less painful, and more esthetic.

Depigmentation in melanomas increases the efficacy of hypericin-mediated photodynamic-induced cell death

Krishna V. Sharma, Lester M. Davids — 2011-10-05

Summary: Melanoma is the main cause of death in skin cancers. Despite combating with early detection, resection and post-operative therapy, melanoma treatment remains unsuccessful and investigations into other forms of adjuvant therapy such as photodynamic therapy (PDT) are prudent. This study proposes that depigmentation i.e. the removal of the free radical scavenging pigment, melanin, in melanotic melanoma cells increases their susceptibility to PDT-induced cell death. Two human melanoma cell lines: one pigmented (Mel-1) and one amelanotic (A375) cell lines were used. Kojic acid (KA), a tyrosinase-specific inhibitor, was optimised to 6μg/ml and shown to quantifiably inhibit melanin synthesis after a 3-day exposure. PDT on these cells resulted in a 3.82 fold increase of intracellular ROS production which correlated to 11% increase in cell death susceptibility compared to untreated controls. Moreover, cells allowed to regain their pigment failed to return to normal even after 72h thus proving the effectiveness of PDT. Using a DPPH* assay, the results confirmed the scavenging properties of melanin (IC50 18.30μg/ml) proving that this pigment may be one of the reasons for melanoma chemoresistance. Overall this study shows that pigment plays an important role in the efficacy of adjunctive PDT treatment and its removal enhances cell death susceptibility in melanomas.

Evaluation of collagen alteration after topical photodynamic therapy (PDT) using second harmonic generation (SHG) microscopy – in vivo study in a mouse model

2012-01-16

Summary: Topical photodynamic therapy (PDT) mediated by 5-aminolevulinic acid (ALA) has been used for the treatment of age-related skin lesions for therapeutic or cosmetic purposes. The modulation of collagen component and structure might play a significant role in influencing treatment outcomes of PDT. In this study, the effect of multi-session low dose ALA PDT on skin rejuvenation was examined in a hairless mouse model. Changes in collagen and skin texture were investigated by histological examination and in vivo second harmonic generation (SHG) microscopy. Results indicated that multi-session PDT could improve the collagen density and arrangement of skin tissue. SHG microscopy combined with quantitative collagen analysis could provide a useful tool for the evaluation of collagen alteration induced by ALA PDT.

mTHPC – A drug on its way from second to third generation photosensitizer?

Mathias O. Senge — 2011-11-02

Summary: 5,10,15,20-Tetrakis(3-hydroxyphenyl)chlorin (mTHPC, Temoporfin) is a widely investigated second generation photosensitizer. Its initial use in solution form (Foscan®) is now complemented by nanoformulations (Fospeg®, Foslip®) and new chemical derivatives related to the basic hydroxyphenylporphyrin framework. Advances in formulation, chemical modifications and targeting strategies open the way for third generation photosensitizers and give an illustrative example for the developmental process of new photoactive drugs.

Research progress of Hemoporfin – Part one: Preclinical study

Yu Pu, Wenhui Chen, Zhengwei Yu — 2011-10-31

Summary: The second generation photosensitizer Hemoporfin (7(12)-(1-methoxyethyl) -12(7)-(1-hydroxyethyl)-3,8,13,17-tetramethyl-21H,23H-porphin-2,18-dipropionic acid) is a porphyrin derivative which processes a stable structure, high singlet oxygen yield, high photoactivity, low dark toxicity and fast clearance rate. Hemoporfin, also known as hematoporphyrin monomethyl ether (HMME) has been studied and used in photodynamic therapy (PDT) in China since 1989. This series of reports will provide an overview on the preclinical and clinical studies of this PDT photosensitizer. The first part of this series will highlight the results of preclinical studies that focused on the compound's optical characteristics, mechanism of the activities, pharmacological and toxicological properties.

Photodynamic therapy of vulvar lichen sclerosus et atrophicus in a woman with hypothyreosis – Case report

B.J. Osiecka, P. Nockowski, K. Jurczyszyn, P. Ziólkowski — 2012-03-29

Summary: Lichen sclerosus et atrophicus (LSA) is disease of skin and mucosa, its pathogenesis remains unknown. Itching, pain and burning sensations and atrophy of vulva impair quality of life. Treatment is symptomatic. We report case of 30-year old woman with lesions in vulva in which series of topical PDT were carried out. We applied Levulan®Kerastick® for 4h and after that lesions were illuminated with red light. Along with above treatment patient started receiving Euthyrox®, because of recently diagnosed hypothyreosis. Significant relief from subjective symptoms was achieved and lesions in vulvar region disappeared. Combination of topical PDT with hormonal therapy allowed controlling course of disease and minimizing symptoms, and thus improved quality of life.