Single Photodynamic Therapy Treatment Research Articles

Lysosome-targeted Aza-BODIPY photosensitizers for anti-cancer photodynamic therapy

Developing effective near-infrared (NIR) photosensitizers (PSs) has been an attractive goal of photodynamic therapy (PDT) for cancer treatment. In this study, we synthesized N, N-diethylaminomethylphenyl-containing Aza-BODIPY photosensitizers and comprehensively investigated their photophysical/photochemical properties, as well as cell-based and animal-based anti-tumor studies. Among them, BDP 1 has strong NIR absorption at 680 nm and higher singlet oxygen yield in PBS which showed favorable pH-activatable and lysosome-targeting ability. BDP 1 could be easily taken up by tumor cells and showed negligible dark activity (IC50 > 50 μM), however strong phototoxicity upon exposure to light irradiation. The acceptable fluorescence emission from BDP 1 allowed convenient in vivo fluorescence imaging for organ distribution studies in mice. After PDT treatment with upon single time PDT treatment at the beginning using relatively low light dose (54 J/ cm2), BDP 1 (2 mg/kg, 0.1 mL) was found to have strong efficacy to inhibit tumor growth and even to ablate off tumor without causing body weight loss. Therefore, pH-activatable and lysosome-targeted PS may become an effective way to develop potent PDT agent.

O2 self-sufficient and glutathione-depleted nanoplatform for amplifying phototherapy synergistic thermodynamic therapy

Tumor hypoxia and high levels of intracellular glutathione (GSH) significantly limit the efficacy of photodynamic therapy (PDT). In addition, a single PDT treatment strategy is relatively insufficient to eliminate tumor, further limiting its application in biomedicine. Therefore, we demonstrated an omnipotent nanoplatform based on 2,2′-azobis [2-(2 imidazolin-2-yl)propane] dihydrochloride (AIPH) loaded manganese dioxide (MnO2) nanoflower (abbreviated as MnO2-AIPH) with simultaneously self-supplying oxygen (O2), depleting GSH, performing PDT, photothermal (PTT) and thermodynamic therapy (TDT) for boosting antitumor effects. By 808 nm near infrared (NIR) light irradiation, MnO2-AIPH not only reveals highly toxic reactive oxygen species (ROS) generation and excellent photothermal conversion ability for PDT and PTT, but also generates alkyl radicals by decomposing AIPH for TDT simultaneously to eliminate tumor effectively. Once internalized into the tumor, MnO2 will be degraded to Mn2+ which catalyzes endogenous hydrogen peroxide (H2O2) into O2 for enhanced PDT. Moreover, MnO2 can facilitate GSH oxidation to amplify oxidative stress, further enhancing ROS and alkyl radicals mediated cancer cell killing. In brief, this study provides a paradigm of antitumor efficiency amplification by the combination of sustained oxygen supply, potent GSH depletion, and phototherapy synergistic TDT.

Clinical Pharmacokinetics and Safety of a 10% Aminolevulinic Acid Hydrochloride Nanoemulsion Gel (BF-200 ALA) in Photodynamic Therapy of Patients Extensively Affected With Actinic Keratosis: Results of 2 Maximal Usage Pharmacokinetic Trials.

The nanoemulsion‐based 10% aminolevulinic acid (ALA) hydrochloride gel BF‐200 ALA optimizes epidermal penetration of its active ingredient and is approved for topical photodynamic therapy (PDT) for the treatment of actinic keratosis in the United States and Europe. To characterize systemic absorption from dermal application during PDT, ALA and its key active metabolite protoporphyrin IX (PpIX) were analyzed in 2 maximal usage pharmacokinetic trials (MUsT) in patients severely affected with actinic keratosis. The primary objective of both MUsTs was to assess baseline‐adjusted plasma concentration–time curves for ALA and PpIX after a single PDT treatment applying either 2 g (1 tube) of BF‐200 ALA on the face (MUsT‐1) or applying 6 g (3 tubes) of BF‐200 ALA on the face/scalp or body periphery (MUsT‐2), to 20 or 60 cm2, respectively. All PDTs were performed using red light at around 635 nm wavelength. Safety and tolerability were documented along with pharmacokinetics. In both MUsTs, ALA plasma concentrations were transiently increased to a maximum concentration at about 2.5 to 3.3 times above endogenous baseline with time to maximum concentration at ≈3 hours after dosing. Plasma levels subsequently returned to baseline within 10 hours after dosing. Overall baseline‐adjusted mean area under the baseline‐adjusted plasma concentration‐time curve from time zero to the last sampling time point at which the concentration was at or above the lower limit of quantification ranged from 142.8 to 146.2, indicating that a similar, minor fraction of topical ALA is systemically absorbed under both dosing regimens. Systemic PpIX exposure after administration of either dose of BF‐200 ALA was equally minimal. Application site skin reactions were treatment area size‐related, albeit transient and consistent with the known safety profile of BF‐200 ALA.

An effective in vivo mitochondria-targeting nanocarrier combined with a π-extended porphyrin-type photosensitizer.

A photochemical reaction mediated by light-activated molecules (photosensitizers) in photodynamic therapy (PDT) causes molecular oxygen to be converted into highly reactive oxygen species (ROS) that are beneficial for cancer therapy. As the active oxygen consumer and the primary regulator of apoptosis, mitochondria are known as an important target for optimizing PDT outcomes. However, most of the clinically used photosensitizers exhibited a poor tumor accumulation profile as well as lack of mitochondria targeting ability. Therefore, by applying a nanocarrier platform, mitochondria-specific delivery of photosensitizers can be materialized. The present research develops an effective mitochondria-targeting liposome-based nanocarrier system (MITO-Porter) encapsulating a π-extended porphyrin-type photosensitizer (rTPA), which results in a significant in vivo antitumor activity. A single PDT treatment of the rTPA–MITO-Porter resulted in a dramatic tumor inhibition against both human and murine tumors that had been xenografted in a mouse model. Furthermore, depolarization of the mitochondrial membrane was observed, implying the damage of the mitochondrial membrane due to the photochemical reaction that occurred specifically in the mitochondria of tumor cells. The findings presented herein serve to verify the significance of the mitochondria-targeted nanocarrier system for advancing the in vivo PDT effectivity in cancer therapy regardless of tumor type.

Ring-Fused Diphenylchlorins as Potent Photosensitizers for Photodynamic Therapy Applications: In Vitro Tumor Cell Biology and in Vivo Chick Embryo Chorioallantoic Membrane Studies.

Ring-fused diphenylchlorins as potent low-dose photosensitizers for photodynamic therapy of bladder carcinoma and esophageal adenocarcinoma are described. All studied molecules were very active against HT1376 urinary bladder carcinoma and OE19 esophageal adenocarcinoma cell lines, showing IC50 values below 50 nM. The in vivo evaluation of the more promising photosensitizer, using an OE19 tumor/chick embryo chorioallantoic membrane model, showed a tumor weight regression of 33% with a single photodynamic therapy treatment with the photosensitizer dose as low as 37 ng/embryo.

PH-Sensitive star-shaped poly(glutamic acid) with a porphyrin core as highly efficient photosensitizers for photodynamic therapy and molecular imaging

Recent efforts to develop tumor-targeted photodynamic therapy (PDT) photosensitizers (PSs) have greatly advanced the potential of PDT in cancer therapy, although complete eradication of tumor cells by PDT alone remains challenging. As a way to improve PDT efficacy, we report a new combinatory PDT therapy technique that specifically targets multilayers of cells. Simply mixing different PDT PSs, even those that target distinct receptors (this may still lead to similar cell-killing pathways), may not achieve ideal therapeutic outcomes. Instead, significantly improved outcomes likely require synergistic therapies that target various cellular pathways. In this study, we target two proteins upregulated in cancers: the cannabinoid CB2 receptor (CB2R, a G-protein coupled receptor) and translocator protein (TSPO, a mitochondria membrane receptor). We found that the CB2R-targeted PS, IR700DX-mbc94, triggered necrotic cell death upon light irradiation, whereas PDT with the TSPO-targeted IR700DX-6T agent led to apoptotic cell death. Both PSs significantly inhibited tumor growth in vivo in a target-specific manner. As expected, the combined CB2R- and TSPO-PDT resulted in enhanced cell killing efficacy and tumor inhibition with lower drug dose. The median survival time of animals with multilayer PDT treatment was extended by as much as 2.8-fold over single PDT treatment. Overall, multilayer PDT provides new opportunities to treat cancers with high efficacy and low side effects.Photodynamic therapy (PDT) is increasingly used as a minimally invasive, controllable and effective therapeutic procedure for cancer treatment. However, complete eradication of tumor cells by PDT alone remains challenging. In this study, we investigate the potential of multilayer PDT in cancer treatment with high efficacy and low side effects. Through PDT targeting two cancer biomarkers located at distinct subcellular localizations, remarkable synergistic effects in cancer cell killing and tumor inhibition were observed in both in vitro and in vivo experiments. This strategy may be widely applied to treat various cancer types by using strategically designed PDT photosensitizers that target corresponding upregulated receptors at tactical subcellular localization.

Multilayer photodynamic therapy for highly effective and safe cancer treatment.

Photodynamic therapy (PDT) is increasingly used as a minimally invasive, controllable and effective therapeutic procedure for cancer treatment. However, complete eradication of tumor cells by PDT alone remains challenging. In this study, we investigate the potential of multilayer PDT in cancer treatment with high efficacy and low side effects. Through PDT targeting two cancer biomarkers located at distinct subcellular localizations, remarkable synergistic effects in cancer cell killing and tumor inhibition were observed in both in vitro and in vivo experiments. This strategy may be widely applied to treat various cancer types by using strategically designed PDT photosensitizers that target corresponding upregulated receptors at tactical subcellular localization.

A case of advanced malignant pleural mesothelioma treatment with chemotherapy and photodynamic therapy.

Malignant pleural mesothelioma (MPM) is an aggressive, treatment-resistant, and generally fatal disease. A 68-year-old male who was diagnosed with MPM at another hospital came to our hospital with dyspnea. We advised him to take combination chemotherapy but he refused to take the treatment. That was because he had already received chemotherapy with supportive care at another hospital but his condition worsened. Thus, we recommended photodynamic therapy (PDT) to deal with the dyspnea and MPM. After PDT, the dyspnea improved and the patient then decided to take the combination chemotherapy. Our patient received chemotherapy using pemetrexed/cisplatin. Afterwards, he received a single PDT treatment and then later took chemotherapy using gemcitabine/cisplatin. The patient showed a survival time of 27 months, which is longer than median survival time in advanced MPM patients. Further research and clinical trials are needed to demonstrate any synergistic effect between the combination chemotherapy and PDT.

P-0085 Locally Advanced/Metastatic Cholangiocarcinoma Treated with Stent, Gemcitabine/Capecitabine Plus-Minus Photodynamic Therapy (Temoporfin) – Preliminary Results From a Norwegian Phase II Trial

IntroductionChemotherapy has been shown to improve survival in patients with locally advanced and metastatic cholangiocarcinoma (CC). Similar data have been reported with photodynamic therapy (PDT) in combination with stent drainage. A combination of these treatment modalities might improve outcomes further, but such data are still lacking. Therefore we have performed the first randomized trial on the combination of temoporfin/PDT, stent and chemotherapy versus stent and chemotherapy only. MethodsRandomized phase II trial with feasibility and toxicity as endpoints. Preliminary data on progression free survival will also be reported. Inclusion criteria were unresectable, treatment naive patients with CC confirmed by histology or cytology, need for biliary stent, bilirubin level<50 mmol/L and no previous cancer disease, ECOG 0-2. The treatment arms were A: stent, temoporfin / PDT followed by Gemcitabine 1000mg/m2 day 1 and 8 and Capecitabine 650 mg/m2 twice daily, day 1-14 every third week (GemCap). A single PDT treatment was given. B: stent, GemCap. Evaluation after every third course including CT scan, MRI and QoL. ResultsTwenty patients with locally advanced and metastatic disease were included, ten patients in each arm. Eight men and twelve women, age 35-75 years. Two patients in arm A did not receive chemotherapy (ECOG>2, infection) and two patients in arm B (thrombocytopenia, study withdrawal). No serious, procedure-related complication was seen. Three cases of cholangitis were observed in both group A and B during the first 30 days. Within the next two months three additional patients in each group had cholangitis, grade 3-4. No liver abscess was observed within 30 days. Within three months, liver abscess was found in two patients, group A. Neutropenia grade 3 was observed in 2 patients in both arms, no neutropenic infection. Preliminary data on progression free survival (three still without progression, one just started) were mean 212 days in group A compared to 162 days in group B. Data on QoL will be reported. ConclusionThe total number of cholangitis was equal in both groups, two abscesses were seen only in group A, more than one month after PDT. No other serious complication related to PDT was seen. Preliminary, progression free survival seems to be prolonged in group A. Depending on the final data a larger study should be considered.

Local treatment of mixed osteolytic/osteoblastic spinal metastases: is photodynamic therapy effective?

The widespread use of systemic and local therapies aimed at spinal metastatic lesions secondary to breast cancer has increased the incidence of mixed osteolytic/osteoblastic patterns of bony disease. The complex structure of these lesions requires novel therapeutic approaches to both reduce tumor burden and restore structural stability. In photodynamic therapy (PDT), a minimally invasive approach can be used to employ light to activate a photosensitizing agent that preferentially accumulates in tumor tissue, leading to cell toxicity and death. Previous work in an osteolytic rat model (MT-1) demonstrated that PDT effectively ablates tumor and improves vertebral structural properties. The aim of this study was to assess the efficacy of PDT in a rat model of mixed osteolytic/osteoblastic spinal metastases. Mixed spinal metastases were generated through intracardiac injection of Ace-1 canine prostate cancer cells into female athymic rats (day 0). A single PDT treatment was applied to lumbar vertebra L2 of tumor-bearing and healthy control rats (day 14). PDT-treated and untreated control rats were euthanized and excised spines imaged with μCT to assess bone quality (day 21). Spines were mechanically tested or histologically processed to assess mechanical integrity, tumor burden, and remodelling properties. Untreated tumor-bearing vertebrae showed large areas of osteolysis and areas of immature, new bone formation. The overall bone quality resulting from these lesions consisted of decreased structural properties but without a significant reduction in mechanical integrity. PDT was shown to significantly decrease tumor burden and osteoclastic activity, thereby improving vertebral bone structural properties. While non-tumor-bearing vertebrae exhibited significantly more new bone formation following PDT, the already heightened level of new bone formation in the mixed tumor-bearing vertebrae was not further increased. As such, the effect of PDT on mixed metastases may be more influenced by suppression of osteoclastic resorption as opposed to the triggering of new bone formation.

Long-term Results of Photodynamic Therapy for Choroidal Neovascularization in Japanese Patients With Pathologic Myopia

To determine the results of photodynamic therapy (PDT) in highly myopic eyes with choroidal neovascularization (CNV). Open-label, consecutive, interventional case series. Forty-eight eyes of 46 consecutive Japanese patients with a myopic CNV were studied. The eyes were treated with PDT and were followed up from 1 to 4 years. The best-corrected visual acuities (BCVAs) at the baseline and after the PDT were compared. Multivariate regression analyses were used to determine the factors that were significantly associated with the BCVA at 3 or 4 years. The mean follow-up period was 3.2 years. Sixty-nine percent of the patients obtained angiographic closure by a single PDT treatment, and the average number of PDT treatments was 1.4. Chorioretinal atrophy developed in 61% of the eyes at 3 years and in 70% of the eyes at 4 years. The BCVA did not change significantly after the PDT. Multivariate regression analyses showed that the BCVA at 3 years was significantly correlated with the baseline BCVA and area of chorioretinal atrophy. Analyses of the 20 patients at 4 years or more showed that in 5 of 7 (71.4%) patients with juxtafoveal CNV, chorioretinal atrophy did not develop and that all had BCVA of 0.5 or better. However, in 12 of the 13 patients with a subfoveal CNV, chorioretinal atrophy developed at 4 years, and 10 of these patients had BCVA of 0.1 or worse. In highly myopic patients, 69% obtained angiographic closure by a single PDT treatment, and recurrence was rare. These findings indicate that PDT is still a good option for treating CNVs in highly myopic patients.

Effects of Photodynamic Therapy on the Structural Integrity of Vertebral Bone

This study investigates the effects of photodynamic therapy (PDT) on the structural integrity of vertebral bone in healthy rats. To determine the short-term (1 week) and intermediate term (6 weeks) effects of a single PDT treatment on the mechanical and structural properties of vertebral bone. Spinal metastasis develops in up to one-third of all cancer patients, compromising the mechanical integrity of the spine and thereby increasing the risk of pathologic fractures and spinal cord damage. PDT has recently been adapted to ablate metastatic tumors in the spine in preclinical animal models. However, little is known about the effects of PDT on the structural integrity of vertebral bone. A single PDT treatment was administered to healthy Wistar rats at photosensitizer and light doses known to be effective in athymic rats bearing human breast cancer metastases. At both 1 and 6 weeks posttreatment, changes in trabecular architecture, global stiffness and strength of vertebrae were quantified using micro-CT stereological analysis and axial compression testing. At 6 weeks, there was a significant increase in bone volume fraction (to 55.7 +/- 11.1% vs. 38.5 +/- 6.4%, P < 0.001) and decrease in bone surface area-to-volume ratio (16.9 +/- 5.0/mm vs. 22.8 +/- 4.5/mm, P = 0.001), attributed to trabecular thickening (130 +/- 40 microm vs. 90 +/- 20 microm, P < 0.001). Similar trends were found at 1 week after PDT. There was a significant increase in stiffness from control (306 +/- 123 N/mm) at 1 week (399 +/- 150 N/mm, P = 0.04) and 6 weeks (410 +/- 113 N/mm, P = 0.05) post PDT. There was a positive trend toward increased ultimate stress at 1 week, which became statistically significant at 6 weeks compared with control (39.3 +/- 11.3 MPa vs. 27.5 +/- 9.5 MPa control, P = 0.002). Not only may PDT be successful in ablating metastatic tumor tissue in the spine, but the positive effects of PDT on bone found in this study suggest that PDT may also improve vertebral mechanical stability.

Beyond bisphosphonates: photodynamic therapy structurally augments metastatically involved vertebrae and destroys tumor tissue

Breast cancer patients commonly develop metastases in the spine, which compromises its mechanical stability and can lead to skeletal related events. The current clinical standard of treatment includes the administration of systemic bisphosphonates (BP) to reduce metastatically induced bone destruction. However, response to BPs can vary both within and between patients, which motivates the need for additional treatment options for spinal metastasis. Photodynamic therapy (PDT) has been shown to be effective at treating metastatic lesions secondary to breast cancer in an athymic rat model, and is proposed as a treatment for spinal metastasis. The objective of this study was to determine the effect of PDT, alone or in combination with previously administered systemic BPs, on the structural and mechanical integrity of both healthy and metastatically involved vertebrae. Human breast carcinoma cells (MT-1) were inoculated into athymic rats (day 0). At 14 days, a single PDT treatment was administered, with and without previous BP treatment at day 7. In addition to causing tumor necrosis in metastatically involved vertebrae, PDT significantly reduced bone loss, resulting in strengthening of the vertebrae compared to untreated controls. Combined treatment with BP + PDT further enhanced bone architecture and strength in both metastatically involved and healthy bone. Overall, the ability of PDT to both ablate malignant tissue and improve the structural integrity of vertebral bone motivates its consideration as a local minimally invasive treatment for spinal metastasis secondary to breast cancer.

The effects of ultra low fluence rate single and repetitive photodynamic therapy on glioma spheroids

Achieving local control of gliomas with photodynamic therapy (PDT) requires the delivery of adequate light fluences to depths of 1-2 cm in the resection margin where the majority of local recurrences originate. This is clinically impractical with current single-shot, intraoperative PDT treatments due to the length of time required to deliver adequate fluences. Multiple or extended treatment protocols would therefore seem to be required. The response of human glioma spheroids to 5-aminolevulinic acid (ALA)-mediated PDT using single or, repetitive light delivery protocols was investigated at both low and ultra low fluence rates. Human glioma spheroids (400 microm diameter) were subjected to sub-threshold light fluence (1.5, 3, or 6 J cm(-2)) ALA-PDT consisting of four light delivery schemes: single treatment given over either 1 or 24 hours, repetitive treatment given either as four 1 hour light treatments separated by a 4 day interval, or 24 hours light delivery, consisting of four 24 hours treatments separated by a 3 day interval. Treatment efficacy was evaluated using a growth assay. In some cases, confocal microscopy was used to image cell viability. The repetitive and single light treatment protocols were most effective when delivered at ultra low (microW cm(-2)) fluence rates. In all cases, growth inhibition was light dose-dependent. The repetitive ultra low fluence rate treatment (1.5 J cm(-2); irradiance = 17 microW cm(-2)) light delivery protocol was the most effective resulting in total growth inhibition during the 2-week observation period. Ultra low light fluence rate ALA-PDT results in significant spheroid growth inhibition. Repeated administration of ALA was required during repetitive and/or protracted single PDT treatment protocols. The existence of a lower fluence rate limit, below which the efficacy of threshold light fluences diminish was not found in these studies. Lasers Surg. Med. 41:578-584, 2009. (c) 2009 Wiley-Liss, Inc.

Optimization of photodynamic therapy with a novel self-adhesive 5-aminolaevulinic acid patch: results of two randomized controlled phase III studies

Photodynamic therapy (PDT) is increasingly used for treatment of actinic keratoses (AKs) but is a cumbersome procedure. A thin self-adhesive patch (PD P 506 A) containing 5-aminolaevulinic acid (5-ALA) was developed to facilitate PDT. To investigate efficacy and safety of the patch in comparison with placebo-PDT (superiority design, observer-blinded; study AK 03) and standard therapy, cryosurgery (noninferiority design, open; study AK 04). Two separate confirmatory randomized parallel-group phase III studies were set up. In total, 449 patients with up to eight mild to moderate AK study lesions located on the head were treated in 29 German study centres (study AK 03: 103 patients; study AK 04: 346 patients). Twelve weeks after treatment, 5-ALA patch-PDT proved to be superior to placebo-PDT (P < 0.001) and cryosurgery (P = 0.007). Efficacy rates on a lesion basis were 82% (AK 03) and 89% (AK 04) for PDT, 77% for cryosurgery and 19% (AK 03) and 29% (AK 04) for placebo-PDT. Local reactions at the treatment site occurred in almost all patients treated with 5-ALA patch-PDT or cryosurgery. Headache was the only side-effect not related to the treatment site which occurred in more than one patient. PD P 506 A is an innovative, easy-to-handle 5-ALA patch for PDT of mild to moderate AK lesions. Compared with current PDT procedures, pretreatment (e.g. curettage) is not needed and handling is considerably facilitated. A single PDT treatment results in efficacy rates being statistically significantly superior to placebo and cryosurgery.

Ocular Changes after Photodynamic Therapy

The aim of this study was to identify the changes in the primate visual system after a single session of photodynamic therapy (PDT) in an intact nonhuman primate retina. As part of a larger study, PDT (wavelength 689 nm, 50 J/cm2, 600 mW/cm2, 83 seconds, 4-mm spot size) with verteporfin (6 mg/m2 intravenous infusion) was performed in one eye each of two cynomolgus monkeys. Fundus photography, fluorescein angiography (FA), indocyanine green angiography (ICG), optical coherence tomography (OCT), and multifocal electroretinography (mfERG) were performed at baseline and 12 time points (1-283 days) after PDT. In addition, retinal histopathologic findings were evaluated at 9 months. Various morphologic changes, including whitening of the treated area, RPE proliferation, closure of the choroidal vasculature, and subretinal edema (followed by foveolar thinning) were observed. Most of the changes persisted and were detectable in histopathologic evaluation at 9 months. Reductions of the mfERG amplitude, followed by varying degrees of recovery from the treated and the border regions, were observed. This was accompanied by progressive delay of P1 peak time up to 3 months after treatment, followed by complete recovery at 9 months. In addition, the nontreated area showed amplitude and timing mfERG deficits, which underwent gradual (but not complete) recovery. In a primate model, under standard clinical parameters, a single PDT treatment resulted in various dynamic morphologic and functional retinal changes detectable for up to 9 months after treatment. The significance of the observed changes and possible ways of pharmacologic interference with PDT adverse effects are discussed.

Pulsed ultrasound measurements of depth and regression of basal cell carcinomas after photodynamic therapy: relationship to probability of 1-year local control

The regression of clinical basal cell carcinoma (BCC) after photodynamic therapy (PDT) is poorly understood, but is potentially important when, as is increasingly the case, a second treatment is contemplated. High-frequency pulsed ultrasound provides noninvasive information on skin and lesion thickness. To relate pulsed ultrasound measurements before and after PDT to the probability of local control of BCC by PDT. Skin thickness and lesion thickness were measured by 20-MHz pulsed ultrasound in 181 patients diagnosed as having BCC. Maximal lesion thickness was determined by repeatedly sampling the BCCs. Measurements were made immediately prior to PDT with aminolaevulinic acid plus 630 nm visible light, and then at 1, 6 and 12 months. Skin thickness in individual patients did not vary with time in this study (mean +/- SD 2.3 +/- 0.6 mm; P = 0.8). In contrast, BCC mean +/- SD maximal thickness 4-6 weeks after PDT was significantly smaller than pretreatment (0.6 +/- 0.8 mm vs. 1.3 +/- 0.8 mm; P < 0.001). The overall probability of 1-year local control fell from 85% when only BCCs </= 1.5 mm thick were considered, to 75% when BCCs up to 3 mm were included. Ultrasound measurement of maximal pretreatment BCC thickness strongly predicts the probability of local control, defined clinically, at 1 year after a single PDT treatment. The degree of regression at 4-6 weeks is additionally predictive.

Photodynamic therapy of feline superficial squamous cell carcinoma using topical 5-aminolaevulinic acid.

A study was undertaken to investigate the treatment of superficial squamous cell carcinoma of the nasal planum, pinna and eyelid in cats by photodynamic therapy, using topical 5-aminolaevulinic acid cream, with subsequent exposure to red light of wavelength 635 nm, supplied by a light-emitting diode source. A total of 13 squamous cell carcinomas were treated, including 10 nasal planum lesions, two pinnal lesions and one eyelid lesion. After a single treatment, complete responses were seen in nine out of 10 nasal planum lesions, one out of two pinnal lesions and the eyelid lesion. The overall complete response rate for lesions managed with a single photodynamic therapy treatment was 85 per cent. Seven of the 11 lesions (63.6 per cent) showing a complete response subsequently recurred; the time to recurrence ranged from 19 to 56 weeks (median 21 weeks, mean 26.7 weeks).

Photodynamic modulation of wound healing with BPD-MA and CASP.

Wound healing is an intricate process requiring the orchestration of cells, growth factors, cytokines, and the extracellular matrix. Cytokines, specifically TGF-beta, are believed to be instrumental in sustaining the fibrotic process, which leads to scarring. Photodynamic therapy (PDT) uses potent photosensitizers, which induce a wide range of effects on cells and the extracellular matrix. The influences of PDT on wound healing are not well known. Seven full-thickness incisional wounds were placed on each of 24 hairless Sprague Dawly rats, three wounds on one flank serving as dark controls and four on the contralateral side treated with PDT. Wounds were created two days before, one hour before, or one hour after red light exposure with an argon ion pumped dye laser. Twelve rats were injected with 0.25 mg/kg or 0.5 mg/kg of the PDT drug, BPD-MA, and the other 12 with 5 mg/kg or 10 mg/kg of the PDT drug, CASP, 3 and 24 hours prior to irradiation of light, respectively. At low doses of both photosensitizers, animals were irradiated with 1, 5, 10, and 20 J/cm2. At higher doses of BPD-MA and CASP animals were treated with 10, 20, 50, and 100 J/cm2 of light. Wounds were examined each day for 14 days and noted for edema, erythema, inflammation, necrosis, and quality of scarring. Wounds were also photographed at day 0, 2, 5, 8, and 14 post-irradiation. All animals were sacrificed 14 days after irradiation and the wounds were evaluated by light microscopy. Grossly, animals treated with 0.25 mg/kg BPD-MA showed no effect with PDT. Animals treated with 0.5 mg/kg BPD, and 5 and 10 mg/kg CASP showed responses that varied with both light and drug dose. Erythema, edema, inflammation, and necrosis attributed to PDT were all observed, but there was no apparent influence of PDT on either the rate or final appearance of wound healing. Histologically, there were no apparent differences between treated and untreated sites, regardless of the drug, dose of light, or time of irradiation. A single PDT treatment given before or after skin wounds does not apparently alter wound healing even when PDT caused brisk inflammatory reactions. PDT may have effects that were not detected. We conclude that PDT does not greatly influence incisional skin wound healing in the rat model.

Photodynamic therapy (PDT) in the treatment of patients with resistant superficial bladder cancer: a long-term experience.

Photodynamic therapy (PDT) combines a photosensitizer such as Photofrin with red laser light (630 nm) to destroy cancer cells. Investigators have reported effectiveness of PDT in the management of patients with recurrent superficial bladder cancer. We retrospectively reviewed our experience in 58 patients to assess the long-term role of PDT in the management of resistant superficial transitional cell carcinoma (TCC) including Ta, T1, and refractory carcinoma in situ (CIS) of the urinary bladder. All 58 patients had failed at least one course of standard intravesical therapy or had contraindication for intravesical chemo- or immunotherapy. Patients with malignancy present (Ta-T1/Grade I-III, CIS) were accepted for ablative PDT. Patients undergoing prophylactic PDT after complete resection were confirmed to be tumor-free by cystoscopy and bladder was cytology before PDT. Post-PDT evaluations included weekly telephone contact to assess acute adverse reactions and assessment of efficacy and bladder toxicity at three months and quarterly thereafter. These 58 patients underwent a single PDT treatment with 2.0 or 1.5 mg/kg of Photofrin and 10-60 J/cm2 light (630 nm). At three months, complete response rates were 84% and 75% for residual resistant papillary TCC and refractory CIS respectively; and 90% of patients treated prophylactically had not had recurrences. At a median followup of 50 months (range 9-110), 59% (34/58) of the responders are alive, with 31/34 still disease-free. PDT using 1.5 mg/kg of Photofrin and 15 J/cm2 of light (630 nm) should be considered a safe and effective treatment for refractory CIS or recurrent papillary TCC.