Monte Carlo Simulations of Light Distributions in an Embedded Tumour Model: Studies of Selectivity in Photodynamic Therapy

. It is well known that photosensitisers in photodynamic therapy (PDT) tend to localise in greater concentrations in tumours. This attractive feature may help confer on PDT the potential to selectivity destroy tumours while sparing the surrounding normal tissue. In this paper Monte Carlo simulations were used to study light distributions in a simple model consisting of tumour embedded in surrounding normal tissue subjected to superficial irradiance. The Monte Carlo model was coded to allow modelling of arbitrary geometries and multiple tissue types. This permitted the use of different optical properties for tumour and normal tissue. Two simulations were run using optical coefficients appropriate to breast carcinoma in adipose tissue and liver tumour in liver. Contours of equal fluence were plotted against depth for both simulations. Contours of equal photodynamic dose (fluence×drug concentration) were plotted for various tumour/normal drug ratios. By assuming a threshold for necrosis it was possible to estimate the depth of damage in the normal tissue and tumour simultaneously. A greater depth of selective tumour damage was observed in the breast tissue simulation for a given drug ratio due to the higher penetration of light compared to the liver. For a tumour to normal ratio of 4:1 selective damage to a depth greater than 4 mm was observed in the breast simulation compared to almost 3 mm in the case of the liver model. Paper received 1 December 1998; accepted after revision 13 July 1999.     

The opportunities of the photodynamic therapy (PDT) in bones' tumours treatment]

The bones tumors represent in orthopedic surgery frequently affection. Among the most often diagnosed primary malignant bones tumors there are: osteosarcoma, chondrosarcoma, gigantocellular tumour of the bone, the Ewing sarcoma. Nearly 35% patients, who start their treatment, have unfortunately, disseminated neoplastic illness (metastases). The much bigger problem (25 times often find than primary neoplasms) are metastatic tumours direct to the bones. Inspite of accessible widespread therapeutic spectrum (multidrugs chemotherapy, surgical tumors' resection, radiotherapy, interferon, genic therapy) five years patients' survival are observed only in small percentage. Therefore, there is a requirement to find more effective and also less invasive method of treatment. The submission of this method seems to be photodynamic therapy (PDT). PDT based on the cytotoxic activity of the laser light and photosensitizer on the neoplastic tissue. Nowdays, there are accepted lines of conduction and closely characterized the indications to PDT in neoplastic diseases. Based on a high grade of efficiency, and also selectivity of PDT, it seems very purposeful to make the investigations about possibilities of PDT in the neoplastic tumours in orthopedics.     

Early morphological changes induced by photodynamic therapy in amelanotic greene melanoma implanted in the anterior eye chamber of rabbits

Morphological changes induced by photodynamic therapy (PDT) in amelanotic Greene melanoma implanted in the anterior eye chamber of rabbits were followed up to 24 h after PDT to study the development of tissue and cell damage leading to necrosis. Immediately after PDT, blood circulation had stopped as shown by fluorescence angiography and light and electron microscopy. It was not restored during the observation period. The first signs of tumour tissue damage, shrinkage of tumour cells and enlargement of intracellular spaces, became apparent immediately after PDT. Tissue and cell destruction increased further, and 24 h after PDT the tumours were almost completely necrotic. The most intriguing finding, by electron microscopy, was the presence of mitochondria with fused membranes in the untreated melanoma cells and the dramatic increase of this aberration directly after PDT. Melanocytes and fibroblasts in the same regions did not exhibit these aberrant mitochondria and furthermore kept a normal fine structure after PDT. Artificially induced ischaemia led to swollen mitochondria with ballooned cristae but showed no increase in membrane fusions. PDT thus directly interferes with mitochondrial structure. Direct damage to tumour cells therefore presumably contributes to tumour necrosis.     

Fluorescence detection of small gastrointestinal tumours: principles, technique, first clinical experience

Photodynamic therapy (PDT) is a form of cancer treatment based on the selective accumulation of a photosensitizer in neoplastic tissue. The fluorescent properties of a photosensitizer permit diagnostic localization of primary tumours and/or metastasis. Occult lesions are hard to detect and can easily be missed during routine laparoscopy. Fluorescence observation offers additional optical information and the ability to detect these occult tumours. Clinically, we used 5-aminolevulinic acid for peritoneal staining and tumour demarcation via tumour-specific fluorescence induced by protoporphyrin IX. For laparoscopic observations, a "D-Light" system was used; the conventional white light source was equipped with an optical blocking filter that transmits at the excitation wavelength (380-450 nm) and blocks all other parts of the spectrum. With the aid of a suitable observation filter, the relevant fluorescence was detectable. With the help of this fluorescence we increased the capacity to detect occult tumours, that were missed with white-light observation (9/26). In the gastrointestinal tract, we used a krypton laser at 405 nm for PP IX fluorescence induction. Although there were high sensitivity rates for neoplasms (81% peritoneal carcinomas, 60% gastric cancer), no exact histopathological statement could be achieved at because of false-positive fluorescence, mainly caused by inflammation (6/32). Current clinical goals and the future perspectives of photodynamic diagnostic are discussed.     

Experimental studies to assess the potential of photodynamic therapy for the treatment of bronchial carcinomas.

BACKGROUND--Photodynamic therapy (PDT) is a technique for producing localised tissue necrosis with light after prior administration of a photosensitising drug. There is some selectivity of uptake of photosensitisers in malignant tissue, although this is difficult to exploit. Full thickness necrosis in normal and neoplastic colon heals without perforation because of a lack of effect on collagen, making local cure a possibility. The experiments described here aim to establish whether these conclusions are also valid for bronchial tumours. METHODS--In pharmacokinetic studies normal rats were given 5 mg/kg of the photosensitiser aluminium sulphonated phthalocyanine (A1SPc) intravenously and killed up to one month later. The distribution of A1SPc in the trachea was measured by chemical extraction and fluorescence microscopy. In subsequent experiments sensitised animals were treated with light delivered to the tracheal mucosa through a thin flexible fibre and the resultant lesions were studied for their size, mechanical strength, and healing. A series of resected human bronchial carcinomas were examined histologically for their collagen content. RESULTS--The tracheal concentration of A1SPc in normal rats was maximum 1-20 hours after administration. Fluorescence microscopy revealed that most was in the perichondrium and submucosal stroma, with little in the cartilage. Light exposure showed necrosis of the soft tissues which healed by regeneration, but no effect on cartilage and no reduction in the mechanical strength of the trachea at any stage. Histological examination of resected human bronchial carcinomas showed more collagen in the tumour areas than would be found in normal regions. CONCLUSIONS--PDT leads to necrosis of the soft tissues of the normal trachea but there is complete healing by regeneration, no risk of perforation (due to collagen preservation), and no effect on cartilage. Human bronchial carcinomas apparently contain more collagen than normal bronchi which may give protection against perforation following necrosis induced by PDT. PDT may have a role in eradicating small volumes of tumour tissue in situ and could be valuable for treating (1) small carcinomas in patients unfit for resection, (2) tumour remaining after surgical resection, (3) stump recurrences, or (4) to prolong palliation of tumours after debulking with the NdYAG laser.     

Damage to Tumour and Brain by Interstitial Photodynamic Therapy in the 9L Rat Tumour Model Comparing Intravenous and Intratumoral Administration of the Photosensitiser

Summary In the 9L rat brain tumour model the damage to tumour and normal brain by photodynamic therapy after intratumoural photosensitizer administration (intratumoural PDT) was studied. Twenty four rats received an intratumoural injection of 4 or 40 mm³ haematoporphyring deriative (HpD, 5 mg ml^–1), followed by interstitial irradiation with 20 Joule (J) (630 nm) 5 h later. For comparison, seven rats were treated with 20 Joule 24 h after an intravenous injection of 10 mg kg^–1 HpD (intravenous PDT). With the chosen PDT parameters there was no important difference between the damaged areas produced by intratumoural PDT or intravenous PDT. No selective tumour kill was observed. Even though normal brain tissue was heavily damaged, vital tumour parts were still present. Intravenous PDT caused extensive diffuse damage to small blood vessels in tumour and surrounding normal brain. Intratumoural PDT was characterised by an infiltration of polymorphonuclear cells into damaged tissue, dilatation of larger blood vessels and gross haemorrhage. These results suggest an immediate vascular shutdown in the intravenous approach, while in the intratumoural approach the vasculature remained patent initially. Because of the severe side effects observed, the use of HpD seems not advisable for intratumoural PDT of brain tumours.     

Preclinical comparison of mTHPC and verteporfin for intracavitary photodynamic therapy of malignant pleural mesothelioma

Efficacy and tumour selectivity of photodynamic therapy with two clinically approved sensitizers (mTHPC, verteporfin) were assessed for focal intracavitary photodynamic therapy (PDT) in rodents with malignant pleural mesothelioma (MPM) at recommended drug-light conditions and at escalating sensitizer dosages. MPM tumours were generated in 15 Fischer rats by subpleural mediastinal tumour cell injection followed after 5 days by intracavitary PDT with light delivery monitored by in situ dosimetry. Animals were intravenously sensitized either with mTHPC (0.1 mg/kg, n = 3; 0.2 mg/kg, n = 3) followed after 4 days by illumination with 20 J/cm(2) at 652 nm, or with verteporfin (0.6 mg/kg, n = 3; 1.2 mg/kg, n = 3) followed after 20 min by illumination with 100 J/cm(2) at 689 nm. Three untreated tumour-bearing animals served as controls. Histological evaluation of the treated tumour and of adjacent normal organs was performed 10 days after tumour implantation. The extent of PDT-induced tumour necrosis was compared to the non-necrosed area and expressed in percentage. A locally invasive growing MPM tumour (3.1 +/- 1 mm diameter) without spontaneous necrosis diameter was found in all animals. For both sensitizers, focal intracavitary PDT was well tolerated at drug-light conditions recommended for clinical applications. Mediastinal organs were spared for both sensitizers but verteporfin resulted in a higher extent of tumour necrosis (80%) than mTHPC (50%). Drug dose escalation revealed a higher extent of PDT-related tumour necrosis for both sensitizers (mTHPC 55%, verteporfin 88%), however, verteporfin-PDT was associated with a higher toxicity than mTHPC-PDT.     

Human pancreatic carcinoma cells are sensitive to photodynamic therapy in vitro and in vivo.

BACKGROUND: The aim of this study was to assess the efficiency of photodynamic therapy (PDT) on human pancreatic cancer cells in vitro and in an animal model. METHODS: Human pancreatic tumour cell lines were submitted to PDT with pheophorbide a (Ph a), a chlorophyll derivative, in culture and after grafting into athymic mice. Ph a was tested in culture (10-10-10-5 mol/l) with a 5-J/cm2 energy treatment and on tumour-bearing Nude mice (30 mg/kg intraperitoneally) with a 100-J/cm2 PDT session. The effect of PDT was assessed in vitro using proliferative, apoptotic and clonogenic tests and in vivo on tumour growth and on the induction of tumour necrosis. RESULTS: PDT inhibited tumour cell growth in culture by affecting DNA integrity. This tumour cell photodamage started at low concentration (10-7 mol/l) as corroborated by clonogenic and tumour growth tests. A strong necrosis was achieved in vivo with a single PDT session. CONCLUSION: PDT destroyed human pancreatic carcinoma after low photosensitizer supply and weak energy application. It exerted this tumoricidal effect via apoptosis induction with a gentle protocol, and apoptosis and/or necrosis with a stronger protocol.     

The effect of photodynamic therapy on rat urinary bladder with orthotopic urothelial carcinoma

OBJECTIVE: To assess the effect of whole-bladder photodynamic therapy (PDT) on a rat model with orthotopic superficial bladder cancer, as PDT is an alternative intravesical therapy for treating superficial bladder cancer, based on an interaction between a photosensitizer and light energy to induce oxygen radicals that destroy tissue by lipid peroxidation. MATERIALS AND METHODS: In all, 76 female Fischer F344 rats were inoculated intravesically with AY-27 tumour cells. After establishing superficial tumour, 24 rats were treated with PDT using aminolaevulinic acid (ALA)-induced protoporphyrin IX as a photosensitizer, and a continuous-wave argon pumped-dye laser (638 nm). At 4 h after intravenous (300 mg/kg) or intravesical (100 mg/mL) administration of ALA the bladders were intravesically exposed to a 40 J/cm(2) light dose; 12 rats received no ALA but were exposed to the same light dose. Before administering ALA, urine cytology samples were taken for analysis. At 3 or 21 days the treated rats were killed and morphological changes in the bladder walls analysed by light microscopy. Forty rats served as controls to examine the presence of tumour. RESULTS: The tumour established in 33 of 40 rats (83%) in the controls, but after PDT with intravesical ALA there was carcinoma in only in one of 12 (P < 0.001, Pearson's chi(2) test). After PDT with intravenous ALA there was carcinoma in five of 11 rats (P = 0.063, Pearson's chi2 test). In the control group of 12 rats receiving only light energy there was carcinoma in three (P = 0.001, Pearson's chi(2) test). Histologically, at 3 days after PDT there was only mild superficial damage in all six rats treated intravesically. Bladder wall destruction reached the muscular layer, with an abscess in one of six rats treated intravenously. After 3 weeks of PDT there was muscular necrosis with perforation and abscess from catheterization two of six rats treated intravesically and in three the bladder wall totally recovered. In the intravenous group the bladder walls were normal or had only mild superficial damage. Cytology of the urine sediment failed to detect half the tumours in the treatment groups. CONCLUSION: These results support the use of PDT with intravesical ALA-induced protoporphyrin X for treating superficial bladder carcinoma. Intravesical was better than intravenous ALA in eradicating bladder carcinoma with PDT.     

Sensitization and photodynamic therapy of normal pancreas,duodenum and bile ducts in the hamster using 5-aminolaevulinic acid

Photodynamic therapy (PDT) using 5-aminolaevulinic-acid-(ALA)-induced protoporphyrin IX (PPIX) increases survival in hamsters with pancreatic cancer. However, experiments with other photosensitizers on this model show a high risk of duodenal perforation. In this paper, the pharmacokinetics and PDT effects of ALA on normal tissues in the pancreatobiliary region are presented. Using quantitative fluorescence microscopy, maximum PPIX fluorescence was seen in the bile ducts, less in the duodenal mucosa and least in the muscularis propria and pancreas. For PDT, light was delivered either using a bare fibre touching the tissue (single-point illumination), or irradiating a 1.5 cm diameter circular area. Single-point PDT (50 J) produced only localized reversible damage without perforation. Surface irradiation of the whole periampullary region (50 J cm^–2) caused extensive damage, sometimes with perforation. Before PDT can be used safely to treat tumours of the pancreas and bile duct, further studies are necessary to understand its effect on larger areas of normal tissue.     

Photodynamic therapy to the oral cavity,tongue and larynx: a canine normal tissue tolerance study

Photodynamic therapy (PDT) has the potential to treat early carcinomas of the oral cavity and larynx while preserving normal tissue. However, normal tissues retain the photosensitizing agents and may be activated by high light fluence and dose rates resulting in normal tissue necrosis. The effects of varying dose rates of light delivery on various tissues in the upper aerodigestive tract have not been evaluated to date and are necessary to determine a therapeutic light dose range that will result in selective tumour necrosis. Thirty adult mongrel dogs received intravenous Photofrin, 2 mg kg^–1, 48 h prior to PDT treatment. Photodynamic therapy was administered to the tongue, buccal mucosa and larynx with a microlens fibre and implantable cylindrical diffuser at various dose rates from 20 to 125 J cm^–2 at 150 mW cm^–2. At the same dose rate of light delivery, the tongue was the most sensitive organ, followed by the buccal mucosa, and last by the larynx. The differential tissue effect of identical dose rates of therapy must be taken into account when administering PDT so that selective tumour necrosis with normal tissue preservation may be achieved. This study indicates the need to perform evaluations of the effect of PDT on other tissue types in an animal model with each new photosensitizer prior to administering PDT to those areas in humans.     

Selective occlusion of choroidal neovascularization by photodynamic therapy with a water-soluble photosensitizer, ATX-S10

BACKGROUND AND OBJECTIVE: To determine the optimal treatment parameters for selective occlusion of choroidal neovascularization (CNV) by photodynamic therapy (PDT) by using the photosensitizer ATX-S10 and a diode laser (wavelength = 670 nm). MATERIALS AND METHODS: Experimental CNV was induced in rat fundi by argon laser photocoagulation. The distribution of ATX-S10 in the chorioretina was analyzed by fluorescence microscopy, and the optimal treatment parameters for selective occlusion of CNV were investigated by changing the dosage and timing of laser irradiation. CNV closure and resulting damage of the surrounding tissue were documented by fluorescein angiography and light and electron microscopies. RESULTS: Fluorescence of ATX-S10 was observed to be localized in the vascular lumen of the retina and choroid within 5 min after dye injection and increased in intensity in CNV up to 2-6 h and decreased rapidly in normal tissue. Laser irradiation with radiant exposures of 7.4 J/cm2 applied immediately after dye injection or with 22.0 J/cm2 at 2-4 h later effectively occluded the induced CNV without causing significant damage to normal retinal capillaries and large choroidal vessels. CONCLUSIONS: PDT using ATX-S10 can selectively occlude CNV. ATX-S10 is a potentially useful photosensitizer for the treatment of CNV.     

Photodynamic treatment of neoplastic lesions of the gastrointestinal tract

Photodynamic therapy (PDT) is a form of cancer treatment based on the selective accumulation of a photosensitizer (by exogenous or endogenous means) in neoplastic tissue. Subsequent activation of the photosensitizer by a specific wavelength of light results in tumor cell death. Activation of a photosensitizer to the appropriate energy state results in the production of singlet oxygen, a powerful oxidizing agent. PDT can kill cells by three mechanisms: direct cell death by photooxidation, apoptosis, or as a consequence of vascular shutdown. The toxicity of PDT is site specific and dependent on the organ being irradiated and the selectivity of the photosensitizer for target tissue over normal tissue. However, there are also reactions related to the sensitizer per se that are independent of those related to the treatment site. Such reactions include cutaneous photosensitization, nausea, vomiting, hypotension, and altered liver 'function' tests. Excitation of photosensitizer by an incident photon produces reemission of a fluorescent photon, which can be used to detect a tumor that is not ordinarily evident. The major limiting factor in using PDT is the depth of tumor kill. The majority of clinical experience involving PDT of the gastrointestinal tract involves patients who are considered to be poor operative risks, and reported follow-ups after treatment are not only limited but also variable.     

Necrosis response to photodynamic therapy using light pulses in the femtosecond regime

One of the clinical limitations of the photodynamic therapy (PDT) is the reduced light penetration into biological tissues. Pulsed lasers may present advantages concerning photodynamic response when compared to continuous wave (CW) lasers operating under the same average power conditions. The aim of this study was to investigate PDT-induced response when using femtosecond laser (FSL) and a first-generation photosensitizer (Photogem) to evaluate the induced depth of necrosis. The in vitro photodegradation of the sensitizer was monitored during illumination either with CW or an FSL as an indirect measurement of the PDT response. Healthy liver of Wistar rats was used to evaluate the tissue response. The photosensitizer was endovenously injected and 30 min after, an energy dose of 150 J?cm^?2 was delivered to the liver surface. We observed that the photodegradation rate evaluated via fluorescence spectroscopy was higher for the FSL illumination. The FSL-PDT produced a necrosis nearly twice as deep when compared to the CW-PDT. An increase of the tissue temperature during the application was measured and was not higher than 2.5 °C for the CW laser and not higher than 4.5 °C for the pulsed laser. FSL should be considered as an alternative in PDT applications for improving the results in the treatment of bulky tumors where higher light penetration is required.     

光动力治疗诱导人胰腺癌细胞凋亡的实验研究

目的 研究光敏剂血卟啉光动力作用对人胰腺癌细胞Panc-1的体外杀伤效应及其主要机制。方法 将光敏剂浓度、光照剂量两个因素按不同水平分组,以CCK-8实验的OD值为检测指标并转换为细胞存活率,研究两个因素对光动力作用的影响及其规律。在此基础上,依次以透射电镜、荧光显微镜、流式细胞仪测定不同处理强度的光动力作用后细胞凋亡及坏死的特点,探讨光动力杀伤肿瘤细胞的主要机制。结果 随着光敏剂浓度和光照剂量的增加,PDT后Panc-1细胞存活率相应下降,但单独给予光敏剂和光照均不对细胞存活率产生影响。PDT后细胞出现凋亡和坏死,二者比例随光敏剂浓度和光照剂量的增加而增加,但始终表现为凋亡率＞坏死率。结论 血卟啉光动力治疗对人胰腺癌细胞株Panc-1具有明确的杀伤作用,但是光敏剂和激光照射本身并不具有独立的杀伤效应。光敏剂浓度、光照剂量两个影响因素在一定范围内与PDT效应之间成正相关的关系。PDT破坏肿瘤细胞的作用机制主要在于诱导细胞凋亡。     

A preliminary experimental in vivo study of the effect of photodynamic therapy on human pituitary adenoma implanted in mice

As surgery alone may prove inadequate to effect a cure for invasive pituitary adenomas, photodynamic therapy (PDT) was investigated as a possible adjuvant treatment for this group of tumours. Different subtypes of human pituitary adenoma cells were implanted subcutaneously into nude mice to study the in vivo effect of PDT on such lesions. The photosensitizer used in this study was polyhaematoporphyrin at a dose of 10 mg/kg b.w., followed by light irradiation at a wavelength of 630 nm with varying light doses between 10 and 75 J/cm2. Histopathological examination of the treated implants consistently showed tumour vascular changes with acute inflammatory reaction, interstitial haemorrhage, and evidence of cell death at higher doses of light. These changes were absent in the control groups. These findings indicate that the cytotoxic effect of PDT demonstrated in vitro in previous studies, is also present in vivo.     

血卟啉衍生物光动力作用杀伤人胰腺癌细胞的实验研究

目的 探讨光动力作用（ＰＤＴ）对体外培养的人胰腺癌细胞的杀伤效应。方法 以２株人胰腺癌细胞系Ｐ３和ＳＷ１９９０为研究对象,采用血卟啉衍生物（ＨＰＤ）作为光敏剂,用高压钠灯（功率密度２５ｍＷ／ｃｍ＾２）为光源,以系列深度的ＨＰＤ经不同剂量的光照后,用ＭＴＴ法测定ＰＤＴ对胰腺癌细胞的相对抑制率。结果 随光敏剂浓度的升高和照光剂的增加,光动力作用对细胞的相对抑制率逐渐增大,在低光动力剂量下明显上升,随后     

Interstitial photodynamic therapy in the Dunning R3327-AT6 prostatic carcinoma

Interstitial photodynamic therapy (PDT) could be an alternative radical treatment for prostate cancer. The ability to predict the depth of necrosis is necessary for light treatment planning using multiple optical fibres. The extent of PDT necrosis was studied in subcutaneously implanted R3327-AT6 Dunning prostate tumours which had similar optical characteristics to human prostate. Tumour-bearing subjects were given 20 mg kg^–1 Haematoporphyrin esters (HPE) and irradiated 24 h later with 630 nm laser light. Five subjects per group were treated with increasing light doses (50–450 J cm^–1) delivered interstitially via a single 2 cm long cylindrical diffuser. After 450 J cm^–1 of irradiation, 4.3±0.8 cm³ [standard error of the mean (s.e.m.)] of tumour tissue was necrosed to a depth of 10.5±0.8 mm around the diffuser. There was an approximately linear correlation between the volume of PDT necrosis around the fibre and prescribed light dose. The mean threshold light dose for PDT effect was 18±2 J cm^–2. In this tumour with a mean photosensitizer concentration of 16±1.5g g^–1, low light doses produced tumour necrosis. PDT using multiple diffusers could destroy a relatively large tumour volume and the diffusion theory model reliably predicted the depth of necrosis.     

Optimizing light dosimetry in photodynamic therapy of the bronchi by fluorescence spectroscopy

Under identical conditions (drug and light dose, timing), the results of photodynamic therapy (PDT) of carcinomas of the bronchi with tetra(meta-hydroxyphenyl)chlorin (mTHPC) show large variations between patients. Before patients underwent PDT treatment, the mTHPC level was measured in the lesion, the normal surrounding tissue and the oral cavity, with an apparatus based on fluorescence spectroscopy. The fluctuations in degree of tissue reaction and tumour destruction between patients could be explained by individual variations in the mTHPC level in the mucosa of the bronchi. The patients who showed the highest mTHPC fluorescence signal also had the strongest response to PDT. In addition, a correlation between the mTHPC level in the oral cavity and bronchial mucosa was found. It is concluded that PDT can be improved by measuring the mTHPC level in the bronchi or the oral cavity before treatment by fluorescence spectroscopy, and then by adjusting the light dose to be applied to the observed mTHPC level.     

The morphological and functional changes in rat bladder following photodynamic therapy with phthalocyanine photosensitization

We have studied photodynamic therapy (PDT) in the rat bladder with a new photosensitizer, aluminium sulfonated phthalocyanine (AlSPc) given intravenously and intravesically. The microscopic distribution of photosensitizer fluorescence in the bladder wall was studied by laser fluorescence microscopy. Prior to PDT the bladder capacity and compliance were assessed by filling cystometry. Intravesical red light (675 nm.) from a copper vapour pumped dye laser was used to activate the photosensitizer using light doses of 20 to 200 J/cm2. Urodynamic and histologic changes were studied at intervals for up to three months. The fluorescence studies showed that AlSPc was eliminated from the deeper muscle layers more quickly than from the superficial layers of the bladder wall so that by 24 hours there was four times as much fluorescence from the mucosa and lamina propria compared to the deeper muscle. Control bladders illuminated with laser light alone showed no effects at these light doses. Animals treated 24 hours after sensitization showed a reduction in bladder capacity of up to 78% (20 J/cm2. light and 1.5 mg./kg.AlSPc). An initial reduction in compliance recovered in two weeks after low doses (0.5 mg./kg.) of AlSPc but was still abnormal at three months after higher doses (1.5 mg./kg.); though there was no long term histologic abnormality seen. Aluminium sulfonated phthalocyanine is a promising photosensitizer for bladder photodynamic therapy and using low doses of the drug it is possible to produce a superficial necrosis without muscle damage across a range of light doses. This heals by epithelial regeneration with no long term functional impairment. Direct absorption of this photosensitizer following intravesical administration seems unreliable.