Photodiagnosis and Photodynamic Therapy

Editorial Board

2011-12-01

Low dose hypericin-PDT induces complete tumor regression in BALB/c mice bearing CT26 colon carcinoma

Renata Sanovic, Thomas Verwanger, Arnulf Hartl, Barbara Krammer — 2011-05-30

Summary: Background: Successful tumor eradication with photodynamic therapy (PDT) in vivo depends on the optimal combination of treatment parameters. (Low-dose) PDT may additionally induce antitumoral immune responses. Since the naturally occurring hypericin (Hyp) is a promising photosensitizer for PDT, the aim of the study was to investigate phototoxic and immunologic effects of a low-dose Hyp-PDT on murine tumors in contrast to commonly used Hyp-PDT conditions.Methods: BALB/c mice bearing CT26 colon carcinoma received hypericin intravenously and were irradiated with red light 0.5–4h later. Tumor development was recorded. Mice were then re-challenged 60 days after the first tumor cell inoculation to investigate an antitumoral immune response.Results: Different results of tumor/host responses were obtained, ranging from mice exitus over delayed tumor growth to complete tumor regression according to different treatment protocols. PDT with common doses and a 4h drug–light-interval resulted in a four times delayed tumor growth compared to the control groups. PDT with relatively low doses and a drug–light-interval of 0.5h led to 100% tumor eradication. Re-challenge of these mice with CT26 mouse colon carcinoma cells prevented new tumor growth.Conclusions: Not only drug concentrations and light doses seem to determine the efficiency of tumor eradication, but also the localization of hypericin at the time of irradiation. Targets in our low-dose PDT protocol are exclusively the vessels. The advantage of this low-dose PDT beside less drug and light exposure of the animals is reduced skin damage, faster healing of the lesions and induction of an antitumoral immune response.

Prospective evaluation of 110 patients following ultrasound-guided photodynamic therapy for deep seated pathologies

2011-09-20

Summary: Introduction: Photodynamic therapy, the fourth oncological interventional modality has proved its success in the management of variety of pathologies involving the human body. Our aim in this prospective clinical study was to continue evaluating the outcome following ultrasound-guided interstitial PDT of pathologies involving the human body. Patients’ reports on quality of life with clinical and radiological evaluation were the main end point parameters used to assess the outcome.Materials and methods: One hundred and ten patients were referred to the UCLH Head and Neck Centre, London for treatment of various deep-seated pathologies. These included tumours in the head and neck as well as vascular anomalies of the limbs. After multidisciplinary discussion, all patients underwent interstitial photodynamic therapy (iPDT) under general anaesthesia, using 0.15mg/kg mTHPC as the photosensitising agent. Following treatment, patients were followed-up for a mean of 26 months.Results: Four out of five patients who presented with visual problems reported improvement after treatment. Also, 27/32 reported improvement of breathing. Improvement of swallowing was reported by 30/37 patients; while speech improvement was evident in 22/29 patients and 43/52 reported reduction in the disfigurement caused by their pathology. Seven out of nine patients with impeded limb function reported some degree of improvement. Clinical assessment showed that nearly half of the patients had “good response” to the treatment and 5 became disease free. Moderate clinical response was reported by 39 patients. Radiological assessment comparing radiological imaging 6-week post-PDT to the baseline showed moderate response in 45 patients and significant response in 32 patients.Conclusion: This study on 110 patients with deep-seated pathologies undergoing interstitial photodynamic therapy provided further evidence that PDT is a useful modality in the management of these pathologies that are otherwise resistant to conventional treatments, and with minimal side effects.

Bioimpedance for pain monitoring during cutaneous photodynamic therapy: Preliminary study

2011-08-16

Summary: Background: Pain is a well-known problem associated with light exposure during topical photodynamic therapy (PDT). Different methods for dealing with the pain have been developed over the past years, ranging from cooling with air or water to nerve blocking. However, the mechanisms responsible for the pain induction have not yet been fully understood.Aim: This study aims to evaluate bioimpedance in situ measurements of human skin as a method to shed light on pain-inducing real-time changes during light exposure during topical PDT.Methods: Cream containing 20% aminolevulinic acid (ALA) was applied on forearms of ten healthy human volunteers. After 24h incubation, the cream was removed and the spots were exposed to red laser light (636nm, 300mW/cm2). During light exposure bioimpedance measurements with a 4-electrode set-up were taken at two frequencies (10Hz and 100kHz).Results: A significant drop in skin impedance at high and low frequencies coincided with onset of pain during light exposure of spots treated with ALA. A similar drop was not observed for controls.Conclusions: Bioimpedance spectroscopy can provide valuable data for real-time observation of changes in skin, and may contribute to an increased understanding of the mechanisms responsible for induction of pain during topical PDT. Future studies are needed.

Effect of photodynamic therapy and endostatin on human glioma xenografts in nude mice

Qi Zhan, Wu Yue, Shaoshan Hu — 2011-05-20

Summary: The aim of this study was to investigate the effect of endostar (a recombinant human endostatin) and photodynamic therapy (PDT) on gliomas. To establish glioma xenografts, human U251 glioma cells were injected into the brain of nude mice. Mice with MRI-confirmed glioma received hematoporphyrin monomethyl ether (HMME)-mediated PDT, daily injection of endostar or their combination, respectively. After treatment, tumor volume, the expression of HIF-1α, VEGF-A and apoptosis marker, and animal survival were examined. PDT and endostar treatment can prolong survival. Changes in induction of apoptosis, tumor growth and survival were more significant in PDT+endostar group. After PDT, HIF-1α and VEGF-A expressions were markedly increased. After endostar treatment, HIF-1α and VEGF-A expressions were significantly reduced. PDT in combination with endostar can significantly inhibit the growth of glioma xenografts. This approach may represent a promising strategy in the treatment of glioma.

Foslip®-based photodynamic therapy as a means to improve wound healing

2011-08-04

Summary: Background: Collagen matrices as substitution for connective tissue are known to promote wound healing. Photodynamic therapy has been anecdotally associated with improved wound healing and reduced scarring. The present study investigates the impact of collagen based scaffolding material, embedded with a liposomal formulation of meta-tetra (hydroxyphenyl) chlorin (mTHPC, Foslip®) and photodynamic therapy on wound healing in mice.Methods: After incision in the neck region, two different types of collagen material, previously incubated with Foslip® at different concentrations, were implanted followed by illumination at 652nm (10J/cm2, 100mW/cm2). Mice were imaged daily up to two weeks, whereafter excision was performed and pathological analysis.Results: Scab detachment was observed at day seven for controls whereas it occurred as early as three days for PDT at the lowest concentrations. In the latter conditions, final matrix remodelling could be observed as evidenced by elastin neosynthesis.Conclusions: Topical application of low dose Foslip® in a collagen matrix followed by illumination considerably accelerates wound healing.

Porphyrins in urine after administration of 5-aminolevulinic acid as a potential tumor marker

2011-06-02

Summary: Background: Tumor markers are commonly used for cancer screening and as indicators of therapeutic effects. Certain types of tumor have been known to produce a variety of porphyrins after 5-aminolevulinic acid (ALA) administration. In this study, porphyrins in tumor-bearing mouse urine were analyzed after oral administration of ALA in order to identify new tumor markers excreted in the urine.Methods: Porphyrin concentrations in the urine of tumor-bearing mice were measured after administration of 1.0mg of ALA (approximately 50mgkg−1).Results: Porphyrin concentrations in the urine of tumor-bearing mice increased after administration of ALA. HPLC analysis of the urine revealed the existence of uroporphyrin (UP) and coproporphyrin (CP) in the urine of ALA-treated tumor-bearing mice. Furthermore, at 3h after ALA administration, UP concentrations in the urine of tumor-bearing mice significantly increased compared to those in the urine of normal mice.Conclusion: These results suggest that UP as a precursor of heme detected in the urine of tumor-bearing mice after ALA administration is a potential marker of tumor development.

In vitro photodynamic inactivation of Candida spp. by different doses of low power laser light

2011-09-19

Summary: This study evaluated the efficacy of PDT in photoinactivation of Candida species using methylene blue (MB) and irradiation with a diode laser (660nm, 40mW). Suspensions of Candida species were obtained containing 106cfu/ml, transferred to 96-holes plates and exposed to 03 doses of laser light (60J/cm2, 120J/cm2, 180J/cm2) in the presence of MB. Additional suspensions were treated with only the MB, the laser light or with 0.85% saline (control groups). After the treatments, 1μl aliquot of the suspensions was plated in duplicate on SDA. The plates were incubated at 37°C for 24–48h and after this period there was the counting of colonies (cfu/ml). The three evaluated doses determined meaningful inactivation of Candida spp. (p<0.05). The 180J/cm2 dose was the most effective, inactivating 78% of cfu/ml. At a dose of 180J/cm2 C. albicans was the most susceptible specie. PDT has demonstrated effectiveness in the inactivation of Candida spp.

Indocyanine green-based photodynamic therapy with 785nm light emitting diode for oral squamous cancer cells

Hyun-Ju Lim, Chung-Hun Oh — 2011-07-13

Summary: Background: The efficiency of photodynamic therapy (PDT) used in combination with Indocyanine green (ICG) and the light emitting diode (LED) on oral cancer was evaluated. The safety risk of ICG is known to be very low and ICG has a strong peak in the vicinity of 700–800nm range which is thought to be a good candidate as a photosensitizer for PDT due to the deep penetration depth into the oral cancer tissue.Methods: The radiation intensity of homemade LED array was 50mW/cm2 at 0.5A. To evaluate the maximum efficiency of ICG-PDT on oral cancer, different wavelengths, ICG concentrations, irradiation interval times after administering ICG, and the time durations after PDT were tested. The cytotoxicity was determined by MTT assay, and apoptosis and necrosis were also observed by double staining with SYTO 16 green and PI.Results: The IC50 value was 10μM when 785nm was irradiated, while it was very low in comparison with 630nm and 895nm. The values were not very different with varying interval time. The percentage of apoptotic cells increased gradually to 84% at 6h after 20μM ICG-PDT and the percentage of necrotic cells dramatically increased to 65% at 3h after 200μM ICG-PDT.Conclusion: Using ICG-PDT with 785nm LED light, the LED is regarded as a satisfying light source since cancer treatments in the oral region do not require focusing and increased depth of penetration due to longer wavelength enhances treatment effectiveness.

Successful treatment of refractory facial acne using repeat short-cycle ALA-PDT: Case study

Hui-Lin Ding, Xiu-Li Wang, Hong-Wei Wang, Zheng Huang — 2011-08-26

Summary: Acne vulgaris is a common dermatological disorder. Topical photodynamic therapy (PDT)-mediated with aminolevulinic acid (ALA) or methyl aminolevulinic acid (MAL) has been successfully used in the treatment of moderate to severe acne. The purpose of this case report is to highlight the feasibility of using a repeat weekly short-cycle ALA-PDT to treat severe facial acne lesions refractory to systemic retinoid and antibiotics.

BMLA 2011, May 19th and 20th Woburn, UK

Kate Dixon — 2011-08-08

The 2011 annual conference of the British Medical Laser Association, with its PDPDT interest group, took place in the splendid setting of Woburn Abbey. The local organisers, Peter Mahaffey and Sue Walker, are to be congratulated for this well orchestrated event.

Chinese Society of Clinical Oncology (CSCO) establishes an Antitumor PDT Expert Committee

Libo Li — 2011-10-05

The 5th CSCO-Nanfang Forum on Tumor Biological Therapy and Molecular Targeted Therapy and the 10th National Symposium on Advances in Comprehensive Cancer Diagnosis and Treatment was held in Guangzhou China on August 21, 2011. During the meeting, Dr. Shukui Qin, the Executive Director of Chinese Society of Clinical Oncology (CSCO), announced the birth of CSCO Antitumor PDT Expert Committee. Drs. Rongcheng Luo and Ying Gu are appointed as the Chairmen of the committee. Drs. Xiaoshan Feng, Yuxian Bai, Nanzheng Zhang, Guoliang Xu and Libo Li are appointed as Vice Chairmen. In addition, the Committee consists of another 24 members. Currently, there are over a dozen oncology expert and specialty committees under the CSCO organization. The addition of a PDT committee reflects the growing interest in Photodiagnosis and Photodynamic Therapy in China.

List of Reviewers Volume 8, 2011

2011-12-01