Photodynamic therapy of experimental tumours with Zn(II)-phthalocyanine and pulsed laser irradiation

The effectiveness of a pulsed dye laser (673 nm) for photodynamic therapy (PDT) of tumours in the presence of Zn(II)-phthalocyanine (ZnPc) was evaluated using Lewis lung carcinoma-bearing mice. The tumours were irradiated with different pulse energies (from 0.4 to 10 mJ) at a constant fluence of 0.6 J cm^–2 at 24 h after administration of 0.25 mg kg^–1 body weight liposome-incorporated ZnPc. Maximal PDT effect, as evaluated by changes in mean tumour diameter, animal survival time and histological evaluation of tumour necrosis, was observed after 3.0 mJ pulse energy irradiation which appears to yield a deeper light penetration and a more efficient sensitizer excitation when compared with lower or higher pulse energies. Electron microscopic analysis of photo-treated tumour indicates preferential damage to malignant tissue as compared to endothelial cells.     

Photodynamic therapy using meso tetra hydroxy phenyl chlorin (mTHPC) in early prostate cancer

BACKGROUND AND OBJECTIVES: Prostate cancer is increasing in incidence, but current treatments including surgery and radiotherapy have significant side effects. This pilot study was designed to assess the potential of photodynamic therapy (PDT) using meso tetra hydroxy phenyl chlorin (mTHPC) for organ confined prostate cancer. STUDY DESIGN/PATIENTS AND METHODS: Six men with organ confined prostate cancer were photosensitised with mTHPC (0.15 mg/kg). Between 2 and 5 days later, red light (652 nm) was delivered to areas of biopsy proven cancer via fibres inserted through transperineal needles (50-100 J per site). RESULTS: After 8 of 10 PDT sessions, the prostate specific antigen (PSA) fell by up to 67%. Early MRI scans showed oedema and patchy necrosis, which resolved over 2 months. Biopsies of treated areas revealed necrosis and fibrosis at 1-2 months. CONCLUSIONS: PDT for primary prostate cancer appears safe and can reduce PSA levels. As this was a phase I study, no attempt was made to treat the whole prostate; this or targeted tumour ablation could be attempted in a phase II study with an increased number of fibres. This technique merits further investigation in early prostate cancer.     

Percutaneous tracheostomy: a clinical comparison of dilatational (Ciaglia) and translaryngeal (Fantoni) techniques.

A number of percutaneous procedures for tracheostomy have been established within the last few years, among them a new technique by Fantoni using a translaryngeal approach for cannula placement. To compare the new translaryngeal tracheostomy (TLT) to the common percutaneous dilatational technique (PDT), we prospectively studied 90 patients who required elective tracheostomy. Tracheostomy was performed according to either the Ciaglia or the Fantoni technique in 45 patients at bedside. The overall complication rate was 11.1% (n = 5) in PDT, including aspiration of blood (n = 4) and severe bleeding requiring surgical intervention (n = 1). During TLT, there were technical difficulties involving guidewire placement in 31.1% (n = 14), and one patient required conversion to PDT. No other complications were noted in TLT. Regardless of the technique used, the postoperative PaO2/FIO2 ratio was slightly lower than preoperatively (P was not significant). When PDT and TLT were compared, the postoperative PaO2/FIO2 ratio was significantly lower in PDT than in TLT (P < 0.05), whereas the preoperative levels did not vary significantly between PDT and TLT. During TLT, the PaCO2 increased significantly, whereas it remained stable throughout PDT. No infection of the tracheostoma was noted in either the PDT or the TLT. We therefore consider both the PDT and the TLT equally safe and attractive techniques for establishing long-term airway access in critically ill patients. IMPLICATIONS: Elective tracheostomy is a widely accepted procedure for gaining long-term airway access. Two techniques for percutaneous tracheostomy-the established Ciaglia method and the new translaryngeal Fantoni technique-were prospectively studied for perioperative complications and practicability in 90 critically ill-patients.     

Photodynamic therapy of tumours and other diseases using porphyrins

Photodynamic therapy (PDT) with porphyrins and red light (620–630 nm) is finding increasing clinical application for both the eradication of relatively small tumours and the palliation of inoperable or obstructive tumours. PDT also shows some promise for the sterilization of the tumour bed after surgical removal of neoplastic masses. Several porphyrins have been found to be accumulated and retained by tumour tissues; however, a chemically prepared derivative of haematoporphyrin, termed HpD, and a purified form of HpD, termed DHE (dihaematoporphyrin ether or ester), are most frequently used in clinical practice owing to their optimal tumour-localizing properties and low systemic toxicity in the dark. The efficiency of HpD/DHE photoactivation by red light is very low, since their extinction coefficient at wavelengths above 600 nm is below 10³ m ⁻¹ cm⁻¹. Therefore, a large number of investigations are being performed in order to improve the efficacy of PDT. One approach involves the use of porphyrin analogs (e.g., chlorins, phthalocyanines) which retain a high affinity for tumours and possess intense absorption bands in the red spectral region. Moreover, the selectivity of tumour targeting can be enhanced by transport of the photosensitizing drug with some types of lipoproteins or monoclonal antibodies. These developments are of interest also in view of the proposed extension of PDT to the treatment of other diseases, including viral and microbial infections, atheroma and psoriasis.     

Tissue distribution of a new photosensitizer ATX-S10Na(II) and effect of a diode laser (670 nm) in photodynamic therapy

The aims of the present study were to analyse the quantitative tissue distribution of ATX-S10Na(II) and to investigate the maximal effect of a diode laser and the irradiation conditions required to obtain this effect in photodynamic therapy (PDT) with ATX-S10Na(II). Spectrofluorometry was used to obtain quantitative tissue distribution of ATX-S10Na(II) in Colon 26 carcinoma-bearing mice as a function of time following administration. Next, transplanted tumours of mice with or without ATX-S10Na(II) were treated with the diode laser under conditions in which power density and irradiation time were varied. Tumour tissue concentrations of ATX-S10Na(II) were higher than in all tissues at all intervals following administration. The uptake of ATX-S10Na(II) by most tissues was rapid, with maximal concentrations occurring 1 h after i.v. injection, and ATX-S10Na(II) was almost excreted within 24 h after administration. The maximal depth of necrosis induced by PDT in the treated tumour was 7.9 mm under conditions in which power density was 160 mW/cm² and total dose was above 100 J/cm². PDT with ATX-S10Na(II) and the diode laser is useful for the treatment of superficial cancers.     

Comparison of laser beam intensity profiles produced by photodynamic therapy (PDT) and transpupillary thermotherapy (TTT) lasers

BACKGROUND AND OBJECTIVES: For photodynamic therapy (PDT) or transpupillary thermotherapy (TTT) lasers, long irradiation time (typically 1 minute or longer) is used and a large area of retina is treated. Consequently, the power stability but also the light distribution within the laser beam plays a major role. This study aimed to evaluate beam intensity profiles produced by several PDT and TTT lasers. STUDY DESIGN/MATERIALS AND METHODS: A beam profile analyzer (Cohu 4812 camera connected to a LPA-300PC, Spiricon, Logan, UT) was used to compare the beam profiles of PDT lasers: OPAL (Lumenis, USA); ACTIVIS (Quantel Medical, France), VISULAS (Zeiss, Germany). Spots of 2, 3, 4, and 5 mm were tested with each laser. Similarly, TTT lasers: OCULIGHT SLx (Iridex, CA) and IRIDIS trade mark (Quantel Medical, France) were evaluated with 2 and 3 mm spot diameter and power ranging from 200 to 1,000 mW. RESULTS: PDT lasers: OPAL had a "top hat" and homogeneous profile whatever the spot size. Numerous micro-spikes and micro-nadirs of power were observed with the ACTIVIS and the VISULAS. TTT lasers: for the IRIDIS the beam shape was rather gaussian, but the homogeneity was reduced by micro-spikes of power. With the OCULIGHT Slx the beam shape was rather top hat and only few micro-spikes or micro-nadirs of power could be disclosed. DISCUSSION: The literature tends to prove that the shape and homogeneity of the beam profile could play a role on the efficacy of the treatment. CONCLUSION: Since PDT and TTT lasers display different beam profiles, this parameter should be carefully evaluated when performing clinical evaluations of PDT or TTT treatments.     

Photodynamic Therapy (PDT) for Oesophageal Dysplasia and Early Carcinoma with mTHPC (m-Tetrahydroxyphenyl Chlorin): A Preliminary Study

Barrett's oesophagus is a premalignant condition in which stratified squamous type mucosa of the normal oesophagus is replaced by specialised intestinal type columnar mucosa. Oesophageal resection was previously considered to be the treatment of choice for high-grade dysplasia or superficial carcinoma arising in this columnar-lined mucosa. We treated four patients with Barrett's oesophagus and high-grade dysplasia, and one patient with superficial oesophageal carcinoma with photodynamic therapy (PDT) using an argon-pumped dye laser light (652 nm). PDT was also delivered using a xenon arc lamp (Paterson lamp, light 652 nm±15 nm) in two patients with Barrett's oesophagus and high-grade dysplasia. mTHPC (m-tetrahydroxyphenyl chlorin) 0.15 mg/kg was used as a photosensitiser in all the patients. We have been able to demonstrate the elimination of columnar-lined oesophageal mucosa, reduction in the length of the Barrett's segment or downgrading of the dysplasia in all of the patients. There is no evidence of recurrence in the patient who had oesophageal carcinoma, at 27 months follow-up. We conclude that mTHPC is useful as a photosensitiser for PDT in the management of Barrett's oesophagus with high-grade dysplasia or superficial carcinoma and the Paterson lamp is a potential alternative light source for PDT. Paper received 5 October 2000; accepted after revision 10 July 2001.     

Cell-cycle-dependent efficacy of photodynamic therapy with ATX-S10(Na)

Photodynamic therapy (PDT) is a useful strategy for treating various cancers. Details of the mechanisms of PDT have not been made clear yet. We intended to study the efficacy of PDT in relation to the cell cycle. HeLa S3 cells were synchronized by the thymidine block method. Cells in different cell cycle phases after release were treated with the water-soluble photosensitizer, ATX-S10(Na). The cellular viability after PDT was determined by the MTT assay. Intracellular levels of ATX-S10(Na) in different cell cycle phases were also determined. We found that cells in the S and G₂/M phases were hypersensitive to PDT with ATX-S10(Na) in comparison with those in the G₁ phase, and that cellular levels of ATX-S10(Na) were increased in cells in the S and G₂/M phases compared to those in the G₁ phase. We conclude that cellular ATX-S10(Na) levels differ among the different cell cycle phases, which is associated with the cell-cycle-dependent efficacy of PDT with ATX-S10(Na).     

Photodynamic therapy with motexafin lutetium (Lu-Tex) reduces experimental graft coronary artery disease.

BACKGROUND: Motexafin lutetium (Lu-Tex) is a photodynamic therapy (PDT) agent that localizes in atheromatous plaque in which it can be activated by far-red light. Lu-Tex biolocalization was examined in graft coronary artery disease (GCAD) with a rodent allograft model. After photoactivation, the effect on intimal proliferation was assessed. METHODS: A PVG to ACI rat heterotopic heart transplantation model was used. Lu-Tex (10 mg/kg) was intravenously administered 90 days after transplantation. Photoactivation was performed 24 hr after Lu-Tex administration. A light-emitting diode, central wavelength of 742 nm, was used to illuminate the intraperitoneally placed allografts via a laparotomy (light fluence of 75 J/cm2 at a power density of 75 mW/cm2). Animals were divided into four groups according to postoperative treatments: PDT with Lu-Tex injection and light illumination (n=21), Lu-Tex injection and laparotomy (n=14), laparotomy with light only (n=14), and laparotomy only (n=16). GCAD was quantitatively assessed 14 days after treatments. RESULTS: Lu-Tex localized in atherosclerotic plaque in vessels with GCAD. PDT significantly reduced both the percent of affected vessels and intimal proliferation compared to all other control study groups. alpha-Smooth muscle cell actin and anti-rat macrophage antibody-positive areas were significantly reduced within the neointima in allografts treated with PDT compared to all other study groups. CONCLUSIONS: PDT significantly reduced atherosclerotic lesions of GCAD. Lu-Tex-mediated PDT may, therefore, be a potential method for treating accelerated atherosclerosis associated with transplantation.     

Photodynamic therapy (PDT) in Barrett's esophagus with dysplasia or early cancer.

OBJECTIVE: Esophagectomy is the standard treatment for high-grade dysplasia (HGD) and intramucosal adenocarcinoma (IMC) arising within Barrett's esophagus. Results of photodynamic therapy (PDT) were retrospectively studied to evaluate the effectiveness of PDT in ablating HGD and/or IMC complicating Barrett's esophagus. METHODS: Thirty-one patients unfit for or refusing esophagectomy (male: 20, mean age: 73.4+/-9.3 years) underwent Porfimer sodium PDT ablation of their HGD (15 patients), HGD plus IMC (10 patients) or submucosal/limited T2 adenocarcinoma (6 patients). The mean Barrett's length was 5.8+/-2.2 cm. Pre-PDT endoscopic mucosal resection or Nd:YAG laser ablation of mucosal nodularity within Barrett's segment was offered in six patients. RESULTS: The main PDT complications were esophagitis (16.1%), photoreactions (12.9%) and stricture requiring dilatation (6.25%). The median post-PDT follow-up was 14 months. The long-term results were (a) for HGD/IMC: initial complete response (endoscopic and histologic absence of HGD-IMC) to PDT was observed in 80.95% of patients, partial response (no endoscopic abnormality, residual IMC-HGD on biopsy) in 9.52%, no response in 9.52% (the recurrence rate after an initial complete response was 17.64%) and (b) for T1b/limited T2 tumors: two patients died from cancer after 24 and 46 months, no evidence of tumor was found in two patients after 12 and 19 months and tumor recurrence was seen in two after 15 and 17 months. The mean survival was 22.1+/-12.3 months. CONCLUSIONS: PDT is effective in ablating HGD/IMC complicating Barrett's esophagus in the majority of cases, while it also seems to be quite effective in treating T1b/limited T2 carcinomas.     

Photodynamic therapy (PDT) in early central lung cancer: a treatment option for patients ineligible for surgical resection

OBJECTIVES: To review the Yorkshire Laser Centre experience with bronchoscopic photodynamic therapy (PDT) in early central lung cancer in subjects not eligible for surgery and to discuss diagnostic problems and the indications for PDT in such cases. METHODS: Of 200 patients undergoing bronchoscopic PDT, 21 had early central lung cancer and were entered into a prospective study. Patients underwent standard investigations including white light bronchoscopy in all and autofluorescence bronchoscopy in 12 of the most recent cases. Indications for bronchoscopic PDT were recurrence/metachronous endobronchial lesions following previous treatment with curative intent in 10 patients (11 lesions), ineligibility for surgery because of poor cardiorespiratory function in 8 patients (9 lesions) and declined consent to operation in 3 patients. PDT consisted of intravenous administration of Photofrin 2 mg/kg followed by bronchoscopic illumination 24-48 h later. RESULTS: 29 treatments were performed in 21 patients (23 lesions). There was no procedure-related or 30 day mortality. One patient developed mild skin photosensitivity. All patients expressed satisfaction with the treatment and had a complete response of variable duration. Six patients died at 3-103 months (mean 39.3), three of which were not as a result of cancer. Fifteen patients were alive at 12-82 months. CONCLUSION: Bronchoscopic PDT in early central lung cancer can achieve long disease-free survival and should be considered as a treatment option in those ineligible for resection. Autofluorescence bronchoscopy is a valuable complementary investigation for identification of synchronous lesions and accurate illumination in bronchoscopic PDT.     

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.     

Combined photodynamic therapy and hyperbaric oxygenation in carcinoma of the esophagus and the esophago-gastric junction

Objectives: The photochemical reaction of photodynamic therapy (PDT) depends on the presence of molecular oxygen. Due to anoxic regions in tumor tissue and vascular shutdown during PDT the efficiency is limited. Therefore, the use of hyperbaric oxygen which increases the oxygen in tumor tissue, as well as the amount of singlet oxygen, may enhance the efficiency of PDT. Patients and methods: After diagnostic work-up, photosensitization was carried out with a hematoporphyrin-derivate 2 mg/kg BW 48 h prior to PDT. The light dose was calculated as 300 J/cm fiber tip. Thirty-one patients were treated by PDT alone and 44 patients received PDT under hyperbaric oxygen at a level of two absolute atmospheric pressure. Results: Improvement regarding stenosis-diameter could be obtained in both treatment arms with no significant difference (P=0.82). The dysphagia-score and tumor-length also decreased in both groups and showed a significant difference in favour of the PDT/HBO-group (P=0.0064 and P=0.0002, respectively). The median overall survival for the PDT-group was 7 months and for the PDT/HBO-group 12 months (P=0.0098). Conclusion: According to this prospective non-randomized study, combined PDT/HBO represents a new approach in the treatment of esophageal and cardia cancer which appears to have enhanced the efficiency of PDT.     

Intraoperative phototherapy (PDT) and surgical resection in a mouse neuroblastoma model

This study evaluates the effect of intraoperative photodynamic therapy (PDT) using the multiline argon laser (488-514 nm) or the argon-dye laser (630 nm) combined with surgical resection compared with surgical resection alone in reducing the incidence of C1300 neuroblastoma recurrence in mice. In the control groups, surgical resection alone resulted in 86% +/- 12% tumor recurrence. Surgical resection and intraoperative lasing without photosensitizer resulted in 75% +/- 27% tumor recurrence with the argon-dye laser and 55% +/- 18% recurrence with the multiline argon laser. In the treatment groups, surgical resection and intraoperative PDT at 630 nm resulted in 56% +/- 19% tumor recurrence whereas surgical resection and intraoperative PDT at 488-514 nm resulted in 21% +/- 7% tumor recurrence. The cause for the decrease in local recurrence in the control group using the multiline argon laser is unknown, but could it be due in part to hyperthermic effects. Intraoperative PDT was an effective adjunct to surgical resection in preventing local recurrence in this tumor model.     

Tetra(m-hydroxyphenyl)chlorin clinical photodynamic therapy of early bronchial and oesophageal cancers

There have been few studies to date of clinical photodynamic therapy (PDT) with tetra(m-hydroxyphenyl)chlorin (mTHPC). This paper describes the results of the authors' experience with this second-generation photosensitizer, used in the treatment of 40 early cancers of the oesophagus and the bronchi. Surface illumination of the tumour was performed, in most cases, 4 days after intravenous injection of 0.15 mg kg^–1 of mTHPC, using 652 nm or 514 nm continuous wave laser light. Endoscopic follow-up with biopsies and brushings was possible for 35 tumours: 27 (77%) showed no recurrence after disease-free follow-ups that ranged from 3 to 38 months. Major complications, all of which were after red light illumination, included one bronchial stenosis, one oesophagotracheal fistula and two probable occult perforations of the oesophagus. Photodynamic therapy with green light renders such perforations of the oesophageal wall essentially impossible at the applied conditions, and appears not to reduce the efficacy of the treatment. Skin photosensitization, which was never observed later than the first week after injection, occurred in 12 patients. Hence, PDT with mTHPC is a safe and effective treatment for early carcinomas of the oesophagus and the tracheobronchial tree.     

Hyperbaric oxygen and photodynamic therapy in the treatment of advanced carcinoma of the cardia and the esophagus

BACKGROUND AND OBJECTIVE: The photochemical reaction of photodynamic therapy (PDT) depends on the presence of molecular oxygen. Because of anoxic regions in tumor tissue and vascular shutdown during PDT, the efficiency is limited. Therefore, the use of hyperbaric oxygen, which increases the oxygen in tumor tissue, as well as the amount of singlet oxygen, may enhance the efficiency of PDT. STUDY DESIGN/MATERIALS AND METHODS: After diagnostic work-up, photosensitization was carried out with a hematoporphyrin-derivate 2 mg/kg body weight 48 hours before PDT. The light dose was calculated as 300 J/cm of fiber tip. Twenty-three patients were treated by PDT alone and 29 patients received PDT under hyperbaric oxygen at a level of two absolute atmospheric pressures. RESULTS: Improvement regarding dysphagia and stenosis-diameter could be obtained in both treatment arms with no significant difference (P = 0.43 and P = 0. 065, respectively). The tumor length also decreased in both groups and showed a significant difference in favour of the PDT/HBO group (P = 0.002). The mean overall survival was 11.3 months. The mean survival time for the PDT group was 8.7 months and for the PDT/HBO group 13.8 months (P = 0.021). CONCLUSION: According to this pilot study, combined PDT/HBO represents a new approach in the treatment of esophageal and cardia cancer, which appears to have enhanced the efficiency of PDT.     

Endobronchial photodynamic therapy for lung cancer

BACKGROUND AND OBJECTIVE: Endobronchial photodynamic therapy (PDT) is a minimally invasive technique for the palliation of major airway obstruction from lung cancer, and for the treatment of endobronchial microinvasive lung cancer. STUDY DESIGN: Results of reported clinical trials were compared, and the author's preliminary results with second generation photosensitizers were also reviewed. RESULTS: A review of the clinical experience with endobronchial PDT is provided. Potential advantages of PDT include the duration of palliation achieved through the delayed cellular effects of PDT within tumor. Side-effects from FDA-approved photosensitizer (Photofrin, Porfimer sodium, Axcan Scandipharm, Montreal, Quebec) include skin photosensitivity. HPPH (2-[1-hexyloxyethyl]-2 devinyl pyropheophorbide) is an example of a second-generation photosensitize that shows promise in the treatment of lung cancer, and appears to be free from significant skin photosensitivity. CONCLUSION: PDT is an effective tool for the palliation of endobronchial lung cancers which obstruct the central airways and is also effective for the treatment of central microinvasive carcinoma and carcinoma in situ of the central airways.     

Photodynamic therapy with photofrin in combination with Buthionine Sulfoximine (BSO) of human glioma in the nude rat

High concentrations of cellular glutathione (GSH) within tumour cells may reduce the ability of photodynamic therapy (PDT) to selectively destroy tumour, consequently, a means of improving the therapeutic ratio of PDT in brain tumour is necessary. Therefore, we hypothesize that PDT in combination with Buthionine Sulfoximine (BSO), an agent which lowers cellular glutathione, can significantly enhance destruction of U87 and U251n tumour cells. PDT was performed using Photofrin as a photosensitiser in combination with BSO administration on male Fisher rats with intracerebral U87 and on non-tumour rats (administered at different optical doses in combination with Photofrin). In vitro experimentation utilising colony forming, cell cytotoxicity, and matrigel artificial basement membrane invasion assays showed significant enhancement of tumour kill and significant reduction of migration in tumour cells treated with BSO in combination with Photofrin PDT in comparison with individual therapies for both U87 and U251n cell lines. In vivo combination PDT-BSO treatment of U87 tumour rats exhibited significantly more tumour necrosis than individual treatments. In conclusion, our data suggests BSO enhances Photofrin PDT treatment of human glioma.     

Photodynamic therapy of malignant brain tumours: a phase I/II trial

Twenty patients bearing malignant brain tumours (18 glioblastoma multiforme, one malignant meningioma, one melanoma metastasis) were treated 25 times with photodynamic therapy (PDT)--the combination of Hematoporophyrin derivative and light at 630 nm (40-120 J/cm2). Sixteen times the PDT was followed immediately by a single dose radiation of 4 Gy of fast electrons. Conventional radiotherapy following PDT was performed in eight patients. The median survival of three patients with multiple recurrences of glioblastoma grade IV and various chemo- and radiotherapy was 5 months. Four out of 10 patients with one recurrence and prior treatment died with a median survival of 5 months, six are still living up to 12 months. Six patients with a primary glioblastoma are surviving now up to 22 months. Phototoxicity to the skin, the only side effect of PDT, was noted in five cases, but did not pose any threat to the patients. The treatment did not affect the quality of life of the patients. Our preliminary results with the photodynamic treatment of malignant gliomas indicate that PDT might be a valuable addition to our armament in the treatment of such tumours.     

Investigation of sequential mitomycin C and photodynamic therapy in a mitomycin-resistant bladder cancer cell-line model

OBJECTIVES: To investigate the hypothesis that sequential mitomycin C and 5-aminolaevulinic acid (ALA)-mediated photodynamic therapy (PDT) interact additively in both the J82 bladder cancer cell line and its mitomycin-C-resistant derivative, J82/MMC, and to assess the theoretical basis of this interaction by measuring the relative mitochondrial density of the respective cell lines, on the basis that the mitochondria are the intracellular site where ALA is metabolized to the active photosensitizer, protoporphyrin IX. MATERIALS AND METHODS: Cell survival was assayed in J82 cell line and the J82/MMC derivative after treating them with sequential ALA-mediated PDT and mitomycin C, and with the sequence of treatments reversed. Cell survival was estimated using the tetrazolium assay. The relative mitochondrial density of the two cell lines was estimated using flow cytometry to measure 123rhodamine fluorescence. RESULTS: The effect of sequential mitomycin C followed by ALA-mediated PDT enhanced the effect of PDT in both cell lines. In J82/MMC this effect was marginally supra-additive. When ALA-mediated PDT was administered before mitomycin C, the combined effect was 'sub-additive'. 123Rhodamine fluorescence was > 10 times greater in J82/MMC than J82, suggesting a significantly higher mitochondrial density in the former than the latter. CONCLUSION: Mitomycin C appears to enhance ALA-mediated PDT when administered first. This appears to be particularly so in J82/MMC. This phenomenon may have clinical significance in recurrent superficial bladder cancer.