Photodiagnosis and Photodynamic Therapy

Editorial Board

2010-06-01

Oncologic photodynamic therapy photosensitizers: A clinical review

Ron R. Allison, Claudio H. Sibata — 2010-04-23

Summary: A myriad of naturally occurring and synthetic structures are capable of transferring the energy of light. Few, however, allow for this energy transfer to enable a type II photochemical reaction which, as currently practiced, is a fundamental component of photodynamic therapy. Even fewer of these agents, aptly termed photosensitizers, have found success in the treatment of patients. This review will focus on the oncologic photosensitizers that have come to clinical trial with outcomes published in peer reviewed journals. Based on a clinical orientation the qualities of successful photosensitizers will be examined, how current drugs fare and potential future options explored.

Photodynamic applications in brain tumors: A comprehensive review of the literature

Sam Eljamel — 2010-03-22

Summary: Introduction: GBM is the comment glioma. GBM-outcome had not changed much over two decades despite leaps in medical technology. Fewer than 25% survive 2 years. There is no jacket that fits all GBMs. This paper reviews the evidence for PDT in GBMs.Rationale: Maximum safe resection is supported by level-II evidence. PDT-technology (PDTT) provides means to maximize safe resection. PDTT paints GBM red in contrast to brain because of selective uptake and retention of photosensitizers. Exposure to specific light wave produces cytotoxic singlet oxygen.PDT-applications: Safety: PDT had a very high safety track record, thromboemolism 2%, brain-oedema 1.3%, and skin photosensitivity complications 1–3%.Conclusion: PDT in GBMs is safe, selective, and sensitive and leads to significant prolongation of good quality survival, delay in tumor relapse and significant reduction of further interventions. It would be impractical, impossible and probably unethical to randomize patients between PDT and placebo, in the same way it would be unethical to carry out a RCT to prove that the parachute saves lives.

Validation of a non-invasive fluorescence imaging system to monitor dermatological PDT

Jessica Tyrrell, Sandra Campbell, Alison Curnow — 2010-04-26

Summary: Background: Methyl-aminolevulinate (MAL) photodynamic therapy (PDT) involves selective accumulation of a photosensitiser, protoporphyrin IX (PpIX), primarily in tumour tissue, which in combination with visible light and tissue oxygen results in reactive oxygen species (ROS) production and thus cellular destruction.Methods: A non-invasive fluorescence imaging system (Dyaderm, Biocam, Germany) has been employed to acquire colour (morphological) and fluorescent (physiological) images simultaneously during dermatological PDT. This system had been previously utilised for fluorescence diagnosis, however, here changes in PpIX concentration within the skin lesions and normal tissue were followed after MAL application. Measurements were also recorded from a synthetic PpIX standard.Results: Results indicated that imaging distance, imaging angle, position of the region of interest and light conditions all altered the PpIX levels acquired from the synthetic PpIX standard. The imaging system was therefore adapted and a standard operating procedure developed allowing reproducible images of dermatological lesions to be acquired. Different concentrations of synthetic PpIX were analysed with the system and a linear relationship was observed between the PpIX concentration and the mean greyscale value calculated for the images acquired up to 10μM.Conclusions: The Dyaderm imaging system can now be used reproducibly with confidence to semi-quantify PpIX (within the range of 0–10μM) within dermatological lesions using the standard operating procedure derived from this work.

Photodynamic inactivation of normal and antifungal resistant Candida species

T.S. Mang, L. Mikulski, R.E. Hall — 2010-04-09

Summary: Background: Susceptibility of bacterial and fungal species to the photodynamic killing effects of various photosensitizing dyes has received increasing attention. In the oral cavity oral candidiasis is primarily caused by Candida albicans. Evidence suggests that Oropharyngeal Candidiasis, found frequently in patients with immunodeficiency, present with mixed Candida organisms and are more difficult to treat than those solely due to C. albicans. In the present study we demonstrate the ability to efficiently kill antifungal resistant isolates of Candida using Photofrin induced PDT.Methods: Candida strains from the ATCC as well as fluconazole and amphotericin B resistant and sensitive isolates from adults with AIDS were grown cultures and grown under standard conditions. Photofrin was added to appropriate cultures as dictated by experimental design. Light was delivered to assigned cultures using a 630nm laser source at a power density of 150mW/cm2, for appropriate time to deliver 45–135J/cm2. Colony forming assays were used to determine survival.Results: After illumination cultures treated with Photofrin had significant reduction in colony forming ability at all light doses examined. Isolates from AIDS patients which had demonstrated antifungal resistance showed equivalent sensitivity to photodynamic killing as did control ATCC cultures of the same strain.Conclusion: This study demonstrates Photofrin induced PDT can eliminate Candida species with significant efficiency as revealed by colony forming ability. Further Candida isolates from AIDS patients that had demonstrated fluconazole and amphotericin B resistance were equally susceptible to photodynamic killing.

Lipophilic photosensitizer administration via the prostate arteries for photodynamic therapy of the canine prostate

2010-04-26

Summary: Background: Current limitations of interstitial photodynamic therapy (PDT) for treatment of prostate cancer include low drug selectivity after intravenous (i.v.) administration and incomplete ablation of glandular tissue. To overcome these limitations, intra-arterial (i.a.) injection of a photosensitizer was tested in a canine model.Methods: A lipophilic photosensitizer, SL052 formulated in liposomes or dissolved in dimethyl sulphoxide (DMSO), was injected into male dogs as an intravenous injection or intra-arterially via the prostate arteries. Optical fibers were inserted into the prostate 3h after i.v. or immediately following i.a. drug delivery. Laser light was delivered through the fibers in cycles controlled by a computer-driven switch. Drug concentration (fluorescence) and light transmission in prostate tissue were monitored during the course of PDT. Side effect profile and completeness of prostate gland ablation were the primary parameters compared among treatment groups. Control animals received drug-only or light-only treatment.Results and conclusion: Thirteen dogs were treated by PDT mediated by i.a. injection of SL052 dissolved in DMSO and attained either complete ablation of prostatic glandular tissue or significant reduction of prostate volume compared with that of pre-PDT (p<0.0001). When compared to i.v. administration the i.a. route resulted in more complete photo-ablation. Associated side effect included acute urinary retention which resolved overtime. No incontinence was observed. With careful tailoring of PDT drug and light doses, interstitial PDT with i.a. injection of SL052-DMSO has the potential to provide effective treatment for prostate disease.

Photodynamic therapy for anal cancer

2010-05-10

Summary: Invasive anal cancers are generally successfully treated by combined chemotherapy with radiation therapy (XRT). For those patients who locally fail this intervention many are salvaged by surgery which generally results in permanent colostomy. We examined the treatment and outcome of Photofrin® based photodynamic therapy (PDT) in a cohort of patients with anal cancer who failed locally despite chemo-radiation (N=6) and two patients with positive margins of resection after excision of small T1 squamous cell anal cancers who refused further surgery or chemo-radiation. PDT consisted of outpatient infusion of Photofrin® at 1.2mg/kg followed 48h later by outpatient illumination. Red light (630nm) illumination was delivered by a 5cm diffusing fiber, treating transphincterally at 300J/cm followed by microlens illumination at 200J/cm2 to the perianal tumor bed with 2cm margin. All patients completed PDT without incident and all have maintained local control of disease in the anal region for the length of follow up (18–48 months). PDT may serve as a new means to salvage local failures and perhaps could be employed as a primary treatment modality in select patients with early stage of disease.

Demonstration of protoporphyrin IX (PpIX) localized to areas of palmar skin injected with 5-aminolevulinic acid (ALA) and pre-treated with a fractionated CO2 laser prior to topically applied ALA

Philip R. Letada, Peter R. Shumaker, Nathan S. Uebelhoer — 2010-03-29

Summary: Background: Several techniques designed to enhance ALA delivery into subcorneal layers of palmar skin are described.Methods: Six palms from three subjects were treated with topical ALA, iontophoresis enhanced delivery of ALA, intradermal injections of ALA solution, or fractionated CO2 laser (with or without erbium:YAG surface ablation). The relative efficacy of each technique was determined using Wood's lamp illumination for the presence of fluorescent PpIX.Results: Palms treated with topically applied ALA alone or with iontophoresis pre-treatment failed to exhibit fluorescence. The palm treated with intradermal injections of ALA and the palms pre-treated with fractionated CO2 laser with or without erbium:YAG laser surface ablation exhibited fluorescence at treatment areas.Conclusion: Both intradermal injections and fractionated CO2 laser (with or without erbium:YAG laser pre-treatment) may provide an effective means for delivery of ALA into subcorneal layers of palmar skin. Numerous potential clinical applications of these techniques (including treatment of localized palmar hyperhidrosis) exist.

Topical treatment of disseminated superficial actinic porokeratosis with hypericin—photodynamic therapy: A case report

Annelies Boiy, Peter A.M. de Witte, Rik Roelandts — 2010-04-01

Summary: Hypericin is a photo-active dye originating from the St. John's wort. Two patients with disseminated superficial actinic porokeratosis (DSAP) were treated with photodynamic therapy (PDT) using topical hypericin. Although a partial response was obtained in one patient topical hypericin-PDT does not emerge as a promising treatment for DSAP.

Endoluminal carotid stenting prior to photodynamic therapy to pericarotid malignant disease: Technical advance

Zaid Hamdoon, Waseem Jerjes, Tahwinder Upile, Parveen Hoonjan, Colin Hopper — 2010-04-09

Summary: We present a technical note which reduces the occurrence of carotid artery rupture during the treatment of peri-carotid disease. The use of radiologically inserted endoluminal carotid stenting prior to photodynamic therapy provides vessel protection.

Lacrimal gland mantle lymphoma treated with photodynamic therapy: Overview and report of a case

Zaid Hamdoon, Waseem Jerjes, Tahwinder Upile, Jonas Osher, Colin Hopper — 2010-04-01

Summary: We present the successful use of interstitial photodynamic therapy in the treatment of lacrimal gland mantle cell lymphoma associated with cervical and axillary lymphadenopathy in a 59-year-old female.

Can surgical site infections be treated by photodynamic therapy?

Michael R. Hamblin, Tianhong Dai — 2010-06-01

In the previous issue of PDPDT , the editor, Prof Keyvan Moghissi raised some interesting points relevant to the question of whether antimicrobial photodynamic therapy (PDT) could ever be used as a clinical treatment for surgical site infections. We should like to answer some of the questions raised in the editorial and make some comments that may shed more light on this intriguing possibility.

Single equipment combines simultaneous application of mechanical ultrasound and photodynamic action for microbial control

J.S.M. Giusti, C.R. Fontana, O.C.C. Guimarães, L.C.P. Pinchemel, V.S. Bagnato — 2010-04-20

An important goal of periodontal therapy is the removal of the bacterial biofilm from the subgingival root surface. The success of mechanical debridement decreases with increasing probing depth and with furcation involvement. Complete removal of bacterial deposits in vivo is accomplished rather seldom, and bacterial reservoirs can survive in mechanically inaccessible areas . Ultrasound technology has been used for a long time by dentists to remove calculus but its association with Photodynamic Therapy (PDT) is a new phenomenon that can facilitate the removal, accelerate the healing process and reduce microorganisms . The development of bright light-emitting diodes (LEDs) made possible the coupling of the two technologies. LED devices have, in general, a lower cost and simpler technology compared to laser devices, and moreover, they can be readily assembled in several configurations that are suitable for different types of anatomical illumination as is necessary for the combination between PDT and ultrasound .