Clinical Studies Of Photodynamic Therapy Research Articles

Validation of multispectral singlet oxygen luminescence dosimetry (MSOLD) for photofrin-mediated photodynamic therapy.

Accurate dosimetry is crucial for the ongoing development and clinical study of photodynamic therapy (PDT). Current dosimetry standards range from less accurate methods involving measurement of only light fluence and photosensitizer concentration during treatment, to significantly improved methods such as singlet oxygen explicit dosimetry (SOED), a macroscopic model that includes an additional important parameter in its dosimetric calculations: ground-state oxygen concentration ([3O2]). However, neither of these models is a method of direct dosimetry. Multispectral singlet oxygen luminescence dosimetry (MSOLD) shows promise in this regard but requires significant improvement in signal quality and remains to be validated in a clinical setting. In this study, we validate a linearly increasing MSOLD signal with an InGaAs photodiode detector for increasing concentration (0 mg/kg to 200 mg/kg) in tissue-simulating phantoms containing photofrin, calculating a calibration curve based on 1270 nm peak-intensity signal and area under the curve for background-subtracted singlet oxygen emission. Additionally, we validate MSOLD against the current clinical dosimetry standard, SOED, through simultaneous measurement of SOED parameters and MSOLD signal for varying concentrations (50 μM - 300 μM). Finally, we investigate the effects of using very high gain amplification on InGaAs photodiode detectors to amplify the MSOLD signal for use in clinical models. We show that a calibration curve relating photosensitizer concentration (PS) and MSOLD signal can be established. Additionally, we demonstrate good correlation between MSOLD signal and SOED-calculated [1O2]rx. However, we show that when using high amplification on InGaAs photodiodes for long illumination times, the inherent instability in these detectors becomes apparent.

Photodynamic therapy of brain tumors and novel optical coherence tomography strategies for in vivo monitoring of cerebral fluid dynamics

Photodynamic therapy (PDT) is a promising tool for least-invasive alternative methods for the treatment of brain tumors. The newly discovered PDT-induced opening of the blood–brain barrier (BBB) permeability open novel strategies for drug-brain delivery during post-surgical treatment of glioblastoma GBM. Here we discuss mechanisms of PDT-mediated opening of the BBB and age differences in PDT-related increase in BBB permeability, including with formation of brain edema. The meningeal lymphatic system plays a crucial role in the mechanism of brain drainage and clearance from metabolites and toxic molecules. We discuss that noninvasive photonic stimulation of fluid clearance via meningeal lymphatic vessels, and application of optical coherence tomography (OCT) for bed-side monitoring of meningeal lymphatic drainage has the promising perspective to be widely applied in both experimental and clinical studies of PDT and improving guidelines of PDT of brain tumors.

Establishment and comparison of three novel methods for the determination of the photodynamic therapy agent 2-[1-hexyloxyethyl]-2-devinyl pyropheophorbide-a (HPPH) in human serum

2-[1-Hexyloxyethyl]-2-devinyl pyropheophorbide-a (HPPH) is a second-generation photosensitizer that has been applied in clinical studies of photodynamic therapy for a variety of malignant lesions. Based on the differences in selectivity and labour intensity, three novel methods – fluorescence detection coupled with high performance liquid chromatography (LC–FLD), LC-tandem mass spectrometry (LC–MS/MS) and fluorescence-based microplate reader methods – were developed for the determination of HPPH in human serum, which allowed comparison of fluorescence and MS platform for HPPH quantification. All three methods have been validated and successfully applied to support the clinical pharmacokinetic study of HPPH. The concentrations measured by LC–FLD matched those by LC–MS/MS with a correlation coefficient (r=0.994) and coefficient of determination (r2=0.989). Data consistency was also found between the measurements of microplate reader and LC–MS/MS with a correlation coefficient (r=0.999) and coefficient of determination (r2=0.998), indicating that fluorescence assay, the low cost alternative with a relatively poorer selectivity, is clearly suitable for the quantification of HPPH. Calibration curves in the methods of LC–FLD and microplate reader were linear (r˃0.998) over the concentration range from 50 to 5000ng/mL, and linearity was obtained over the concentration range from 5 to 1000ng/mL in the LC–MS/MS method. Compared with the other two methods, the fluorescence-based microplate reader method with proven high selectivity should be strongly recommended because of obvious advantages such as the lowest labour intensity, the lowest instrument cost, a better sensitivity than LC–FLD and the very rapid determination of large number of samples (24 samples/40s).

A clinical study of photodynamic therapy for chronic skin ulcers in lower limbs infected with Pseudomonas aeruginosa.

The objective of this study is to evaluate the antimicrobial activity and healing-promoting effect of topical photodynamic therapy (ALA-PDT) on chronic skin ulcers infected with Pseudomonas aeruginosa (PA). A total of 26 patients with chronic skin ulcers in lower limbs infected with PA were enrolled. The surface areas of the ulcers were treated with either δ-aminolevulinic acid (ALA)-mediated PDT (20% ALA solution, 1.5 h incubation, 630 nm red light, 80 J/cm(2)) or red light alone, both once a week for two weeks. Before treatment, the wound areas and the bacteria levels in these two groups were comparable (p > 0.05). Results indicated that the bacteria levels in the skin ulcers of the light only group of 24 h post-treatment (3.4 × 10(7) ± 7.1 × 10(7) CFU/cm(2)) and pre-treatment (5.5 × 10(7) ± 1.6 × 10(8) CFU/cm(2)) were not significantly different. In contrast, the bacteria levels on the surfaces of the ulcers in the PDT group of 24 h post-treatment (6.3 × 10(5) ± 1.7 × 10(6) CFU/cm(2)) and pre-treatment (8.9 × 10(7) ± 1.7 × 10(8) CFU/cm(2)) were significantly different (p < 0.01). At seven days post treatment, the mean ulcer area in the red light group was reduced from 11.85 ± 6.83 to 7.8 ± 4.9 cm(2) (p < 0.01), that of PDT group from 12.72 ± 8.58 to 3.4 ± 3.4 cm(2) (p < 0.01). Better healing was seen in PDT group (p < 0.01). In conclusion, ALA-PDT is a potential modality to control PA infection and promote healing of chronic skin ulcers in lower limbs.

Synthesis, radiolabeling, biodistribution and fluorescent imaging of histidine-coupled hematoporphyrin

Hematoporphyrin (Hp) and hematoporphyrin derivatives (HpDs) have been widely used as photosensitizers in photodynamic therapy (PDT). Radiolabeling of HpDs is helpful for preclinical and clinical studies of PDT. The histidine-coupled hematoporphyrin (His-Hp) was synthesized and radiolabeled with [(99m)Tc(CO)(3)(H(2)O)(3)](+). Biodistribution of the radioligand and fluorescent imaging of His-Hp in mice bearing S180 tumor were investigated. [(99m)Tc(CO)(3)](+)-labeled His-Hp was electrically neutral, hydrophilic and stable. The biodistribution of the radioligand in S180 tumor-bearing mice was similar with that of nonlabeled HpD in the literature. The uptake of His-Hp in tumors and livers was confirmed by fluorescent imaging. The complex [(99m)Tc(CO)(3)](+)-His-Hp might be suitable for in vivo dose evaluation of HpD in PDT.

バイオフィルム対策としてのレーザーの応用―歯周治療におけるＰＤＴの現状―

The main etiologic factor of periodontitis is the dental biofilm in the periodontal pockets. Biofilm is formed by the glycocalyx structure. Recently, the fundamental studies of photodynamic therapy (PDT) which used laser devices and photosensitizers to periodontal treatment have been reported. The advantage of PDT is that it can only affect the target tissue by combination of laser light with a specific wavelength to activate a photosensitizer and this photosensitizer does not have any toxicity. Therefore, the heat effect from laser device to other tissues becomes weak. Additional, it may be possible to destroy biofilm in the pocket where the laser fiber can not reach and evade side effects such as antibiotic. In this paper, the various clinical studies of photodynamic therapy (PDT) which have been reported until now and our studies are introduced. The possibility of application to periodontal treatment of PDT is also discussed.

Clinical study of photodynamic therapy with visudyne for polypoidal choroidal vasculopathy

To study the clinical effect of photodynamic therapy (PDT) with Visudyne for polypoidal choroidal vasculopathy (PCV). Ten patients (10 eyes) with PCV who were diagnosed by fundus fluorescein angiography (FFA), indocyanine green angiography (ICGA), optic coherence tomography (OCT) were treated by PDT with Visudyne. Eight cases (8 eyes) were male, the other two cases (2 eyes) were female. Their ages ranged from 50 to 77 years, mean (59.5 +/- 9.70) years. The best corrected visual activity (BCVA) before PDT was 0.1 - 0.5. The changes of BCVA, fundus photography, FFA and ICGA before and after PDT were compared. Follow-up time varied from 6 months to 36 months, mean 24 months. 1 month after PDT the BCVA was found to be unchanged in 4 eyes, increased in 1 line in 3 eyes, increased in 2 lines in 2 eyes, decreased in 3 lines in 1 eye. FFA and/or ICGA showed no leakage in 4 eyes, leakage reduced in 3 eyes, slight leakage in 2 eyes. At the last follow-up, the BCVA was found to be unchanged in 4 eyes, increased in 1 line in 2 eyes, increased in 2 lines in 2 eyes, increased in 3 lines in 1 eye which received 3 times PDT, decreased in 2 lines in 1 eye. FFA/ICGA showed no leakage in 7 eyes, slight leakage in 2 eyes. No systemic or local adverse effect was found during or after PDT, except 1 eye with extensive subretinal hemorrhage suffered vitreous hemorrhage one month after PDT. Photodynamic therapy with Visudyne may stop or reduce the macular leakage, facilitate the absorption of hemorrhage, exudates and edema, stabilize or increase the patients' visual activities. It could be a choice for the treatment of PCV. Certainly these tendencies need to be confirmed in a multi-center randomized controlled investigation with longer follow-up time.

Methylene blue mediated laser therapy of maxillary sinusitis

The purpose of the present work is a clinical study of photodynamic therapy of maxillary sinusitis. 0.1%-Methylene Blue aqueous solution in combination with He-Ne laser irradiation (632.8 nm) have been used for treatment of maxillary sinus mucous of patients with acute and chronic maxillary sinusitis. The differences between the results of the treatment with dye and light versus treatment with a drug for every group of patients were statistically analyzed by Student’s t test. The efficacy of the photodynamic therapy was estimated with the use of the following criteria: the state of respiration, olfaction, duration of purulent discharge, reconstruction of transport function of ciliary epithelium, etc. The obtained results have shown that the photodynamic therapy is effective in comparison with conservative methods of treatment of the disease.

Clinical Study of Photodynamic Therapy for Upper Gastrointestinal Tract Cancers

Objective: To evaluate the clinical effectiveness and adverse effects of photodynamic therapy (PDT) for the upper gastrointestinal tract cancers. Methods: 56 patients with upper gastrointestinal cancers in different clinical stages were treated with PDT. Diode laser (630 nm) was used as the light source and the parameters were as follows: power density 200 to 400 mW/cm, energy density 100 to 300 J/cm. PHOTOFRIN was used as photosensitizer, which was given in a dose of 2 mg/kg intravenously 12-24 h before irradiation. Results: Evaluation of the 56 patients' therapeutic effectiveness showed that 6 patients (10.7%) had a complete response (CR), 33 patients (58.9%) partial response (PR), 12 patients (21.4%) mild response (MR), and 5 patients (8.9%) no response (NR). The total response rate (CR+PR) was 69.6%. No patients had severe adverse effects in this group. Conclusion: PDT is an effective and safe palliative modality for upper gastrointestinal tract cancers.

Photodynamic Therapy for Pancreatic and Biliary Tract Carcinoma

The prognosis of patients with pancreatic and biliary tract cancer treated with conventional therapies such as stent insertion or chemotherapy is often poor, and new approaches are urgently needed. Surgery is the only curative treatment but is appropriate in less than 20% of cases, and even then it is associated with a 5-yr survival of less than 30% in selected series. Photodynamic therapy represents a novel treatment for pancreaticobiliary malignancy. It is a way of producing localized tissue necrosis with light, most conveniently from a low-power, red laser, after prior administration of a photosensitizing agent, thereby initiating a non-thermal cytotoxic effect and tissue necrosis. This review outlines the mechanisms of action of photodynamic therapy including direct cell death, vascular injury, and immune system activation, and summarizes the results of preclinical and clinical studies of photodynamic therapy for pancreaticobiliary malignancy.

Phase II clinical study of photodynamic therapy using mono- l-aspartyl chlorin e6 and diode laser for early superficial squamous cell carcinoma of the lung

Photofrin is the most commonly used photosensitizer for photodynamic therapy (PDT). The major side effect of Photofrin is cutaneous photosensitivity. A second generation photosensitizer, mono- l-aspartyl chlorin e6 (NPe6) has shown anti-tumor efficacy and rapid clearance from skin. Therefore, we conducted a phase II clinical study to investigate the anti-tumor effects and safety of NPe6 in patients with early superficial squamous cell carcinoma of the lung. Enrollment criteria consisted of endoscopically evaluated early stage lung cancer with normal chest X-ray and CT images, no lymph node or distant metastasis. Tumors were located no more peripherally than subsegmental bronchi, the peripheral margin had to visible, and the tumor size had to not more than 2 cm in diameter. The histologic type of the tumor had to squamous cell carcinoma. Laser irradiation (100 J/cm 2) using a diode laser was performed at 4 h after administration of NPe6 (40 mg/m 2). Among 41 patients with 46 lesions, 40 with 45 lesions were eligible for safety evaluation, and 35 patients with 39 lesions were judged as eligible for efficacy evaluation. No serious adverse drug reactions were observed. Disappearance of skin photosensitivity was recognized within 2 weeks in 28 of 33 patients (84.8%) and in all the other seven patients first tested at 15–18 days. Complete response (CR) was seen in 84.6% of lesions (82.9% of patients). This study demonstrated excellent anti-tumor effects and safety, especially low skin photosensitivity in patients with early stage lung cancer. PDT using the second generation photosensitizer NPe6 and a diode laser will likely become a standard modality of PDT for central type early superficial squamous cell carcinoma of the lung.

A Clinical Study of Photodynamic Therapy for Superficial Esophageal Carcinoma by YAG-OPO Laser

A cooperative clinical study of photodynamic therapy (PDT) for superficial esophageal carcinoma was conducted at 6 medical institution. PHE (2mg/kg) with high tumor affinity was used as the oncotropic compound. The light source was a pulse wave YAG-OPO laser with high penetration into the tissue. Irradiation was performed at an energy density of 60–180 J/cm2 48–72 h after PHE administration. Eight lesions in 6 patients were treated. All were type 0-II superficial carcinomas. The depth of invasion was EP–MM for 6 lesions and SM for 2 lesions. A complete response (CR) was achieved in all patients after one session of PDT. Five adverse events, including anemia and fever, were reported by 4 patients, but all were WHO grade 2 or lower and transient. PDT using PHE and YAG-OPO laser was therefore considered effective as a curative therapy for superficial esophageal carcinoma.

Clinical study of Photodynamic Therapy for Head and Neck Cancer

Photodynamic therapy (PDT) is a recently developed treatment involving the use of a photosensitizer and low power light, usually from a laser, to selectively destroy tumor cells. At present, we perform PDT for head and neck cancer using excimer dye lasers with hematoporphyrin derivative as a photosensitizer. This study attempted to assess the utility and safety of PDT and to investigate the long-term outcome. All 24 patients had squamous cell carcinoma : 15 with laryngeal, 5 with lingual or oral, and 4 with pharyngeal cancer and were treated by PDT. Data were obtained from records from February 1988 through April 1995. Following PDT, 12 of 15 laryngeal cases were classified as complete remissin (CR ), as were 3 of the 5 lingual or oral, and one of the 4 pharyngeal cancer patients. The longest duration of CR in cases treated by PDT alone was 89 months. Photosensitivity was experienced by all patients, but required no treatment. Liver, kidneys and bone marrow showed no abnormal values. There were no clinically relevant adverse reactions and patients with severe complications due to other types of treatment and elderly patients were also treated safely with this therapy.

Clinical studies of photodynamic therapy for roentgenographically occult lung cancer

Clinical studies of photodynamic therapy for roentgenographically occult lung cancer

Photodynamic therapy in head and neck surgery

The results of a clinical study of photodynamic therapy (PDT) on early stage cancer in head and neck surgery are presented in this report. 30 patients with T 1 malignancies of the face and oropharynx have been treated primarily with PDT. After the longest follow up of 14 months two patients revealed recurrence of the disease or residual tumor, two patients have been retreated because of residual dysplastic cells in the control biopsy, and all other patients stay histologically proven free of disease. Hence, PDT appears to be a promising cancer treatment for different histological tumors that penetrate the host tissue definitely less than a laser beam of 630 nm, which is the appropriate wavelength for PDT. Deeper-penetrating malignomas may be accessable for PDT using insertable filters when applying interstitial laser light.