Periorbital skin cancers subjected to mTHPC-photodynamic therapy: A prospective study.

INTRODUCTION: Photodynamic therapy (PDT) is a relatively new method of treating skin cancers. This prospective study highlights the use of PDT in the management of basal cell carcinomas (BCCs) and T1N0 cutaneous squamous cell carcinomas (SCCs) involving the periorbital area. MATERIALS AND METHODS: Surface illumination PDT was offered under local anaesthesia. mTHPC was administered intravenously. A single-channel 652 nm diode laser was used for illumination, and light was delivered at 20 J/cm2 per site. Lesion response evaluation was carried out according to response evaluation criteria in solid tumours (RECIST). RESULTS: After the first round of treatment, all cutaneous T1N0 SCC patients had complete response (CR) and continued to be in remission until last clinic review. For BCC patients, 12/14 patients had CR. The two remaining patients underwent a second round of treatment and also achieved a CR. All BCC patients were in remission at the last clinic review. Using visual analogue scale (VAS), 15 patients reported that this treatment gave them "excellent" cosmetic outcome (VAS 9-10). CONCLUSION: Photodynamic therapy achieved high efficacy in the treatment of periorbital BCCs and cutaneous SCCs with greatly reduced morbidity and disfigurement.

Evaluation of mTHPC-loaded PLGA nanoparticles for in vitro photodynamic therapy on C6 glioma cell line.

Photodynamic therapy (PDT) is a very attractive strategy to complement or replace common cancer treatments such as radiotherapy, surgery, and chemotherapy. Some molecules have shown their efficiency as photosensitizers (PS), still many issues have to be solved such as the inherent cytotoxicity of the PS or its hydrophobic properties causing limitation in their solubility, leading to side effects. In this study, the encapsulation of an approved PS, the meso-tetra hydroxyphenylchlorine (mTHPC, Foscan®) within biocompatible and biodegradable poly(D, l-lactide-co-glycolide) acid (PLGA) NPs prepared by the nanoprecipitation method was studied. The mTHPC-loaded NPs (mTHPC ⊂ PLGA NPs) were analyzed by UV-vis spectroscopy to determine the efficiency of mTHPC encapsulation, and by dynamic light scattering (DLS) and atomic force microscopy (AFM) to determine mTHPC ⊂ PLGA NPs sizes, morphologies and surface charges. The longitudinal follow-up of mTHPC release from the NPs indicated that 50% of the encapsulated PS was retained within the NP matrix after a period of five days. Finally, the cytotoxicity and the phototoxicity of the mTHPC ⊂ PLGA NPs were determined in murine C6 glioma cell lines and compared to the ones of mTHPC alone. The studies showed a strong decrease of mTHPC cytotoxicity and an increase of mTHPC photo-cytotoxicity when mTHPC was encapsulated. In order to have a better insight of the underlying cellular mechanisms that governed cell death after mTHPC ⊂ PLGA NPs incubation and irradiation, annexin V staining tests were performed. The results indicated that apoptosis was the main cell death mechanism.

Online dosimetry for temoporfin-mediated interstitial photodynamic therapy using the canine prostate as model.

Online light dosimetry with real-time feedback was applied for temoporfin-mediated interstitial photodynamic therapy (PDT) of dog prostate. The aim was to investigate the performance of online dosimetry by studying the correlation between light dose plans and the tissue response, i.e., extent of induced tissue necrosis and damage to surrounding organs at risk. Light-dose planning software provided dose plans, including light source positions and light doses, based on ultrasound images. A laser instrument provided therapeutic light and dosimetric measurements. The procedure was designed to closely emulate the procedure for whole-prostate PDT in humans with prostate cancer. Nine healthy dogs were subjected to the procedure according to a light-dose escalation plan. About 0.15 mg/kg temoporfin was administered 72 h before the procedure. The results of the procedure were assessed by magnetic resonance imaging, and gross pathology and histopathology of excised tissue. Light dose planning and online dosimetry clearly resulted in more focused effect and less damage to surrounding tissue than interstitial PDT without dosimetry. A light energy dose-response relationship was established where the threshold dose to induce prostate gland necrosis was estimated from 20 to 30 J/cm2.

Efficacy and safety of photodynamic therapy with temoporfin in curative treatment of recurrent carcinoma of the oral cavity and oropharynx.

Therapeutic options for recurrent carcinoma of the upper aérodigestive tract (UADT) are limited. The prognosis of these tumours remains poor with significant rate of recurrence and a lower median survival time. Photodynamic therapy (PDT) is a relatively new therapeutic alternative which combines the use of a photosensitising agent and light to induce a cytotoxic effect on the tissues. This is a retrospective single-centre study carried out in patients with a recurrence of an oral cavity or oropharyngeal carcinoma or a second appearance of tumour in a previously irradiated area. There were no metastases in lymph nodes or other organs. Laser treatment was carried out 96 h after temoporfin (Foscan(®)) injection. In our series we had 14 cases with a complete response, 1 partial response. Overall survival at 1 year was 72 % and 36 % at 5 years. Disease-specific survival at 1 year was 82 % and 45 % at 5 years. Recurrence-free survival at 1 year was 52 % and 34 % at 5 years. Side effects mainly described are pain in the area of illumination, well controlled. PDT with Foscan(®) gives useful results in terms of survival and improvement in quality of life with few adverse events or severe complications. The fact that it has low toxicity and that treatment sessions can be repeated mean it should be considered in the therapeutic armamentarium for recurrent carcinoma of the UADT.

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

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 6 h. For the IPDT+antioxidant experiments, P. halepensis was injected intratumourously 1 h 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 15 J 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.

Improved photodynamic cancer treatment by folate-conjugated polymeric micelles in a KB xenografted animal model.

Photodynamic therapy (PDT) is a light-induced chemical reaction that produces localized tissue damage for the treatment of cancers and various nonmalignant conditions. In the clinic, patients treated with PDT should be kept away from direct sunlight or strong indoor lighting to avoid skin phototoxicity. In a previous study, it was demonstrated that the skin phototoxicity of meta-tetra(hydroxyphenyl)chlorin (m-THPC), a photosensitizer used in the clinic, can be significantly reduced after micellar encapsulation; however, no improvement in antitumor efficacy was observed. In this work, a folate-conjugated polymeric m-THPC delivery system is developed for improving tumor targeting of the photosensitizer, preventing photodamage to the healthy tissue, and increasing the effectiveness of the photosensitizers. The results demonstrate that folate-conjugated m-THPC-loaded micelles with particle sizes around 100 nm are taken up and accumulated by folate receptor-overexpressed KB cells in vitro and in vivo, and their PDT has no significant adverse effects on the body weight of mice. After an extended delivery time, a single dose of folate-conjugated m-THPC-loaded micelles has higher antitumor effects (tumor growth inhibition = 92%) through inhibition of cell proliferation and reduction of vessel density than free m-THPC or m-THPC-loaded micelles at an equivalent m-THPC concentration of 0.3 mg kg(-1) after irradiation. Furthermore, folate-conjugated m-THPC-loaded micelles at only 0.2 mg kg(-1) m-THPC have a similar antitumor efficacy to m-THPC or m-THPC-loaded micelles with the m-THPC concentration at 0.3 mg kg(-1) , which indicates that the folate conjugation on the micellar photosensitizer apparently reduces the requirement of m-THPC for PDT. Thus, folate-conjugated m-THPC-loaded micelles with improved selectivity via folate-folate receptor interactions have the potential to reduce, not only the skin photosensitivity, but also the drug dose requirement for clinical PDT.

Peripheral neural cell sensitivity to mTHPC-mediated photodynamic therapy in a 3D in vitro model.

BACKGROUND: The effect of photodynamic therapy (PDT) on neural cells is important when tumours are within or adjacent to the nervous system. The purpose of this study was to investigate PDT using the photosensitiser, meta-tetrahydroxyphenyl chlorin (mTHPC), on rat neurons and satellite glia, compared with human adenocarcinoma cells (MCF-7). METHODS: Fluorescence microscopy confirmed that mTHPC was incorporated into all three cell types. Sensitivity of cells exposed to mTHPC-PDT (0-10 microg ml(-1)) was determined in a novel 3-dimensional collagen gel culture system. Cell death was quantified using propidium iodide and cell types were distinguished using immunocytochemistry. In some cases, neuron survival was confirmed by measuring subsequent neurite growth in monolayer culture. RESULTS: MCF-7s and satellite glia were significantly more sensitive to PDT than neurons. Importantly, 4 microg ml(-1) mTHPC-PDT caused no significant neuron death compared with untreated controls but was sufficient to elicit substantial cell death in the other cell types. Initially, treatment reduced neurite length; neurons then extended neurites equivalent to those of untreated controls. The protocol was validated using hypericin (0-3 microg ml(-1)), which caused neuron death equivalent to other cell types. CONCLUSION: Neurons in culture can survive mTHPC-PDT under conditions sufficient to kill tumour cells and other nervous system cells.

Optimization of treatment parameters for Foscan-PDT of basal cell carcinomas.

BACKGROUND AND OBJECTIVE: Basal cell carcinomas (BCCs) are the most common form of skin cancers with high and increasing incidence rates. Photodynamic therapy (PDT) with mTHPC (Foscan) has shown to be a promising treatment alternative with good cosmetic results. The current study was aimed to determine optimal treatment parameters for this indication. STUDY DESIGN/MATERIALS AND METHODS: mTHPC-PDT was performed in 117 patients with a total of 460 BCCs with diagnosis confirmed by scratch cytology. Treatment parameters were altered as follows: Foscan dose 0.03-0.15 mg/kg, drug-light interval (DLI) 1-96 hours, total energy density 20-120 J/cm(2). Outcomes were assessed 8 weeks post-PDT following WHO guidelines. RESULTS: The overall rate of complete remissions (CR) was 96.7% and the cosmetic outcome was very good. In the largest subgroup (n=80) where low-dose Foscan was applied (0.05 mg/kg mTHPC; 48 hours DLI; 50 J/cm(2) total energy density), a CR rate of 100% with a high and narrow 95% Confidence Interval of 0.955-1.000 was achieved. Smaller variations of the treatment parameters (i.e., reducing the photosensitizer dose to 0.04 mg/kg or shortening the DLI to 24 hours) yielded similarly good results. Side effects were encountered in 52 out of 133 PDT sessions. They were more common in patients who had received high drug doses (0.06-0.15 mg/kg) and comprised mostly pain and phototoxic reactions. Three patients developed severe sunburns with subsequent scarring at the injection site following bright sunlight exposure 15-19 days after photosensitizer administration. CONCLUSIONS: The presented data suggest that mTHPC-PDT with the treatment parameters mentioned above seems to be an effective treatment option for BCCs. If sensibly applied, it is well tolerated and provides mostly excellent cosmetic results. Long-term results are yet to be evaluated.

Photodynamic therapy of feline cutaneous squamous cell carcinoma using a newly developed liposomal photosensitizer: preliminary results concerning drug safety and efficacy.

BACKGROUND: Squamous cell carcinomas are common skin tumors in cats. We investigated photodynamic therapy (PDT) using a new liposomal photosensitizer as a minimally invasive, effective treatment that can be easily performed while achieving good cosmetic results. AIM: The goal of this study was to assess and describe possible toxicities using a liposomal formulation of the photosensitizer meta-(Tetrahydroxyphenyl)Chlorin (m-THPC) and investigate if favorable pharmacokinetics translate into favorable tumor response and control. ANIMALS: Eighteen client-owned cats with 20 spontaneous cutaneous squamous cell carcinomas were included in the study. METHODS: PDT was performed using a new, liposomal formulation of the photosensitizer. Toxicity, tumor response, and tumor control were evaluated retrospectively. RESULTS: No general adverse effects were observed in cats treated with the new liposomal formulation. Mild local toxicity such as erythema and edema were seen in 15% of the patients. All cats responded to therapy, with a complete response rate of 100%. The overall 1-year control rate was 75%. The tumor recurrence rate was 20% with a median time to recurrence of 172.25 +/-87.1) days. CONCLUSIONS AND CLINICAL IMPORTANCE: A new liposomal photosensitizer was successfully used for squamous cell carcinoma in cats and was well tolerated. There were no systemic adverse effects observed with the liposomal formulation. The favorable pharmacokinetics of the liposomal drug resulted in a favorable tumor response.

Photodynamic therapy of malignant biliary strictures using meso-tetrahydroxyphenylchlorin.

OBJECTIVES: The palliation of patients with malignant bile duct obstruction using metal or plastic biliary stents may be limited by stent occlusion. The aim of this study was to determine the safety and efficacy of endoscopically delivered meso-tetrahydroxyphenyl chlorin photodynamic therapy in the treatment of irresectable malignant biliary strictures and recurrent stent occlusion. METHODS: Thirteen patients with malignant biliary obstruction owing to carcinoma of the biliary tract (n=9), pancreas (n=3) or stomach (n=1), were studied. All had been initially palliated with metal (n=10) or polyethylene (n=3) biliary stents, but presented with recurrent obstructive jaundice because of local tumour progression. Patients received meso-tetrahydroxyphenyl chlorin 0.15 mg/kg intravenously 72 h before endoluminal light activation with an endoscopically placed optical fibre, followed by polyethylene stent insertion. RESULTS: Before photodynamic therapy, patients had a median of three (range 0-5) stent occlusions in the preceding 11 (2-22) months, with a median patency of plastic stents placed inside metal bile duct stents for recurrent stent occlusion of 3.5 (0.5-13) months. After photodynamic treatment, tumour necrosis and/or metal stent recanalization was seen in all patients, with a median of 0 (0-3) stent occlusions during 7 (1-43) months follow-up. The median patency of plastic stents placed inside metal stents after photodynamic therapy was 5 (1-43) months. The median survival after diagnosis and photodynamic therapy administration was 21 (10-56) and 8 (1-43) months, respectively. Photodynamic therapy was generally well tolerated but two patients developed cholangitis within the first week, complicated in one by a fatal liver abscess and two developed haemobilia within 4 weeks of treatment, one of whom died with a gall bladder empyema. CONCLUSION: In patients with malignant biliary obstruction, endoscopically delivered meso-tetrahydroxyphenyl chlorin photodynamic therapy causes efficient tumour necrosis and recanalization of blocked metal stents, but there is a significant risk of complications.

Photodynamic therapy in normal pig stomach: protective effect of octreotide.

BACKGROUND AND STUDY AIMS: Many factors, such as oxygen and vasculature, are involved in the cytotoxic effect of photodynamic therapy (PDT). It is known that somatostatin and its analog octreotide decrease the splanchnic blood flow and have multiple inhibitory effects in different functions of the peptic system. The aim of this experimental study was to assess the effect of octreotide administration on PDT outcome in normal pig stomach. METHODS: 28 healthy pigs, randomly assigned to two groups, A and B, were studied. Pigs in both groups were sensitized with 0.3 mg/kg intravenous meta-tetra (hydroxyphenyl) chlorin (m-THPC), and 48 hours later light of wavelength 650 nm was delivered from a 50-mW diode laser for 300 s (energy fluence 15 J/cm (2)) through a gastroscope to the gastric mucosa. Group A underwent PDT without octreotide and group B had PDT with administration of octreotide. At 72 h after light delivery, all the animals were sacrificed for macroscopic and histological evaluation of the irradiated site. RESULTS: The macroscopic images and the histology of the stomach PDT lesions (inflammation, ulceration, necrosis) showed significantly less severity in the group of animals with octreotide injection (group B). In this group, full-thickness necrosis was observed in 28.5 %, compared with over 71.4 % in group A; this was statistically significant ( P < 0.05). CONCLUSION: Octreotide may have a modulating effect on m-TPHC PDT in normal gastric tissue in pigs, probably due to alterations of hemodynamics in the stomach and to suppression of the inflammatory process.

mTHPC-mediated photodynamic therapy for early oral squamous cell carcinoma.

Surgery and radiotherapy are standard treatments for early oral squamous cell carcinoma, both resulting in good tumour control. However, neither of these modalities is without consequent functional or cosmetic impairment, and there are patients in whom both are contraindicated. Furthermore, there is a significant risk of metachronous tumours developing in the oral cavity, and salvage or retreatment with either surgery or radiotherapy poses difficulties. Photodynamic therapy (PDT) offers the potential for improved functional and cosmetic outcomes, while achieving comparable tumour control. We conducted an open-label, multicentre study to assess the efficacy and safety of meta-tetrahydroxyphenylchlorin (mTHPC) in patients with early oral cancer. One hundred twenty-one patients received intravenously administered mTHPC, followed 96 hr later by illumination of the tumour surface with 652 nm laser light. Of these patients, 114 were protocol compliant. A complete tumour response was achieved in 85% of protocol-compliant patients (97 of 114 patients). A complete response was maintained in 85% of responders at 1 year and in 77% at 2 years. One- and 2-year actuarial survival rates were 89% and 75%, respectively. In the opinion of the investigators, tumour clearance was accompanied by excellent cosmetic and functional results, without impact on the patients' performance status. Mild-to-moderate pain at the treatment site, a recognised side effect of PDT in the oral cavity, was reported by 82% of patients but was manageable with appropriate analgesia. Mild-to-moderate skin photosensitivity reactions were reported for 13% of patients. mTHPC offers an effective alternative treatment for early oral squamous cell carcinoma. It is associated with excellent functional and cosmetic results and can be used in conjunction with other standard therapies.

Photodynamic therapy with green light and m-tetrahydroxyphenyl chlorin for intramucosal adenocarcinoma and high-grade dysplasia in Barrett's esophagus.

BACKGROUND: The eradication of early stage neoplastic lesions in Barrett's esophagus is imperative to prevent invasive adenocarcinoma. Early stage lesions have an extremely low risk of lymph node metastasis, thereby, making local treatment feasible. Photodynamic therapy destroys malignant cells by a photochemical effect. The aims of this study were to evaluate the efficacy and tolerance of photodynamic therapy with green light and a new photosensitizer, temoporfin or m-tetrahydroxyphenyl chlorin in patients with Barrett's esophagus and early stage neoplastic lesions. METHODS: Four days after injection of m-tetrahydroxyphenyl chlorin, lesions were illuminated at a wavelength of 514 nm through non-circumferential windowed diffusers. Follow-up endoscopy with biopsies was performed at regular intervals. RESULTS: Fourteen lesions (7 high-grade dysplasia, 7 intramucosal adenocarcinoma) in 12 patients were treated. For all lesions, efficacy was 100% and squamous re-epithelialization was complete. Side effects were of moderate severity (one stricture). Mean follow-up was 34 (15) months (range 12-68 months). CONCLUSIONS: Green light photodynamic therapy with m-tetrahydroxyphenyl chlorin can eradicate early stage neoplastic lesions in Barrett's esophagus and may be proposed as an alternative first-line therapy or a second-line therapy after failure of other endoscopic treatments. The efficacy and patient tolerance of the procedure justify further studies of the method in larger groups of patients.

Experimental evaluation of possible side effects of intra-operative photodynamic therapy on rabbit blood vessels and nerves.

BACKGROUND AND OBJECTIVES: Tumours of the head and neck show a high local tumour recurrence rate ranging between 7 and 30% despite combined treatment modalities. To improve these data, photodynamic therapy (PDT) might be used as an additional treatment besides surgery and radio-chemotherapy. Intra-operative PDT has been proposed to "sterilise" the tumour bed after surgical tumour resection in order to kill any remaining tumour cells which are responsible for local tumour recurrences. Often, during head and neck surgery, large blood vessels and important nerve structures are exposed and could potentially be harmed by intra-operative PDT. Despite the fact that mTHPC is the most commonly used photosensitiser for head and neck tumours, there are no data on potential detrimental side effects of intra-operative PDT onto these vital structures. The purpose of this study was to use a maximal treatment protocol in rabbit observing possible damage to the blood vessels and nerve structures and thus judge the most severe event that could happen in patients. STUDY DESIGN/MATERIALS AND METHODS: In rabbits the large blood vessels and nerve structures at the neck and at the groin area were surgically exposed and treated by mTHPC-mediated intra-operative PDT. Various treatment parameters (drug-light interval, light dosage, follow up interval) were modified in order to find the critical treatment parameters which might cause maximum tissue effects. The intention was to define the most severe clinical complications which could be expected from mTHPC mediated intra-operative PDT. RESULTS: The most severe tissue reactions were found at a drug dosage of 0.3 mg/kg, a drug-light interval of 24 hours and a light dosage of 20 J/cm(2). Complete necrosis was found for the muscles, fat and connective tissue within the entire treatment field. Blood vessels demonstrated severe oedema, media-hyperplasia or loosening of the endothelial layer leading to various degrees of local thrombosis but no break down of the vessel wall or any rupture was noted. Most nerves were altered by a 75% demyelisation but this did not result in any clinical symptoms. CONCLUSIONS: Our results have shown that mTHPC mediated intra-operative PDT used with a maximal treatment protocol (very high doses and very short drug-light intervals) has significant histological impact onto all tissue structures, but did not show any clinical symptoms in rabbits. mTHPC mediated intra-operative PDT seems to be a promising and a safe treatment option which could complement existing treatment modalities in order to improve total survival rate of tumour patients.

A phase I study of Foscan-mediated photodynamic therapy and surgery in patients with mesothelioma.

BACKGROUND: Photodynamic therapy (PDT) is a light-based cancer treatment that, in the correct setting, can be delivered intraoperatively as an adjuvant therapy. A phase I clinical trial combining surgical debulking with Foscan-mediated PDT was performed in patients with malignant pleural mesothelioma. The purpose of the study was to define the toxicities and to determine the maximally tolerated dose (MTD) of Foscan-mediated PDT. METHODS: A total of 26 patients completed treatment. Tumor debulking was accomplished with either an extrapleural pneumonectomy (7 patients) or a lung-sparing pleurectomy-decortication (19 patients). Patients were injected with Foscan before surgery, and 652 nm light was delivered intraoperatively after completion of surgical debulking. Four light sensors were placed in the chest, allowing delivery of light to a uniform measured dose throughout the hemithorax. RESULTS: Four dose levels were explored. The MTD was 0.1 mg/kg of Foscan injected 6 days before surgery in combination with 10 J x cm(-2) 652 nm light. Dose limiting toxicity at the next higher dose was a systemic capillary leak syndrome leading to death in 2 of 3 patients treated at that dose. Other PDT-related toxicities included wound burns and skin photosensitivity. In all, 14 patients were treated at the MTD without significant complications. CONCLUSIONS: Foscan-mediated PDT can be safely combined with surgery at the established MTD. Unlike most other surgery-based multimodal treatments for mesothelioma, Foscan-mediated PDT affords the option, in selected patients, of accomplishing tumor debulking with a lung-sparing procedure rather than an extrapleural pneumonectomy. A phase II study is warranted.

Photodynamic therapy for prostate cancer recurrence after radiotherapy: a phase I study.

PURPOSE: Photodynamic therapy, using a photosensitizing drug activated by red light, can destroy localized areas of cancer with safe healing and without the cumulative toxicity associated with ionizing radiation. We used photodynamic therapy in a phase I-II study to treat patients with locally recurrent prostate cancer after radiotherapy. MATERIALS AND METHODS: Patients with an increasing prostate specific antigen (PSA) and biopsy proven local recurrence after radiotherapy were offered photodynamic therapy. Three days after intravenous administration of the photosensitizer meso-tetrahydroxyphenyl chlorin, light was applied using optical fibers inserted percutaneously through perineal needles positioned in the prostate with imaging guidance. Patients were followed with PSA measurements, prostate biopsies, computerized tomography or magnetic resonance imaging and questionnaires on urinary and sexual function. RESULTS: Photodynamic therapy was given to 14 men using high light doses in 13. Treatment was well tolerated. PSA decreased in 9 patients (to undetectable levels in 2) and 5 had no viable tumor on posttreatment biopsies. After photodynamic therapy, contrast enhanced computerized tomography or magnetic resonance imaging showed necrosis involving up to 91% of the prostate cross section. In 4 men stress incontinence developed (troublesome in 2 and mild in 2) which is slowly improving. Sexual potency was impaired in 4 of the 7 men able to have intercourse before photodynamic therapy, which did not improve. There were no rectal complications directly related to photodynamic therapy, but in 1 patient a urethrorectal fistula developed following an ill-advised rectal biopsy 1 month after therapy. CONCLUSIONS: Photodynamic therapy is a new option that could be suitable for organ confined prostate cancer recurrence after radiotherapy. With more precise light dosimetry, it may be possible to destroy essentially all glandular tissue within the prostate with few complications. These results suggest that photodynamic therapy merits further investigation.

Tissue levels, histologic changes and plasma pharmacokinetics of meta-Tetra (hydroxyphenyl) chlorin (mTHPC) in the cat.

The biodistribution and pharmacokinetics of meta-tetra(hydroxyphenyl)chlorin (mTHPC)(1) have been documented in humans, rats, dogs and rabbits. It has been demonstrated to be an effective photodynamic therapy agent for treatment of squamous cell carcinoma. Squamous cell carcinoma is a common feline neoplasm, causing significant morbidity and mortality in the feline population. The association between ultraviolet radiation exposure and occurrence of this neoplasm in the cat provides a useful model for the study of human cutaneous squamous cell carcinoma. In this study, we document the biodistribution, pharmacokinetics and toxicity of mTHPC in a group of normal cats. Four groups of cats were given the drug intravenously at dosages of 0, 0.15, 0.30 and 0.60 mg/kg. mTHPC levels were measured in plasma and tissues at 0, 24, 48, 72, 96 and 336 h after drug administration. Additionally, plasma samples were collected at 1 and 6 h post-injection and analysed. Biodistribution and pharmacokinetics of mTHPC in cats mirrors that in other animal species. There were no clinical or pathological changes associated with administration of the drug. The biodistribution and pharmacokinetics of mTHPC in cats mirrors that in other species studied. There were no clinical or pathological changes attributable to administration of the drug at the doses administered. mTHPC may be a useful photodynamic therapy drug in cats.

Comparison of the in vivo efficiency of photofrin II-, mTHPC-, mTHPC-PEG- and mTHPCnPEG-mediated PDT in a human xenografted head and neck carcinoma.

BACKGROUND AND OBJECTIVE: One of the approaches to enhance the selectivity and efficiency of photodynamic therapy (PDT) was the conjugation of the photosensitizer meta-tetrahydroxyphenylchlorin (mTHPC) to the water-soluble polymer polyethylene glycol (PEG). Several studies have demonstrated that mTHPC-PEG has a higher selectivity and a longer circulating half-life than free mTHPC, whereas no in vivo effect of this benefit could be seen. STUDY DESIGN/MATERIALS AND METHODS: In a model of RAG-2-mice bearing a human oral squamous cell carcinoma xenograft (XF 354), the in vivo efficiency assessed as growth retardation or remission caused by Photofrin II and free mTHPC was compared with mTHPC coupled in two different ways to polyethylene glycol (PEG). One hundred and fourty-nine female RAG-2-mice were randomised into one control group and 13 therapy groups. Treatment parameters were adapted from those routinely applied in animal studies. RESULTS: Photofrin II-mediated PDT and mTHPC-mediated PDT were both in vivo highly effective, whereas mTHPC induced less scars. The in vivo results after mTHPC-PEG-mediated PDT were disappointing, whereas the effectiveness of mTHPCnPEG-mediated PDT, a newly coupled macromolecular photosensitizer, were promising. CONCLUSIONS: These results demonstrated the impact of the method of linkage between the photoactive agent mTHPC and polyethylene glycol (PEG) upon the in vivo effectiveness. mTHPC and mTHPCnPEG are promising photosensitizers for the future, especially for the cosmetic treatment needs of head and neck surgery.