Peritumoural Tissue Research Articles

Tissue plasminogen activator expression in meningiomas and glioblastomas

Objectives: Enzyme-linked immunosorbent assay (ELISA) and Western blotting techniques were used to investigate and compare the expression of tissue plasminogen activator (tPA) in benign (meningioma) and malignant (glioblastoma) human brain tumours. Methods: A total of 22 tumour samples comprising 11 meningiomas and 11 glioblastomas with adjacent peritumoural tissue were analysed. Results: The mean tPA content of meningiomas was approximately half that of glioblastomas (55.40 (S.D. 34.58) versus 106.98 (S.D. 43.82) ng/ml, p = 0.006). Comparing tPA quantity in tumour and peritumoural tissue, there was a significant difference for meningiomas (55.40 (S.D. 34.58) versus 28.35 (S.D. 22.55) ng/ml, p = 0.05), but no difference for glioblastomas (106.98 (S.D. 43.82) versus 84.23 (S.D. 57.39) ng/ml, p = 0.32). Comparing tumour with normal brain tissue, there was no difference for meningiomas (55.40 (S.D. 34.58) versus 33.08 (S.D. 21.55) ng/ml, p = 0.22), but a significant difference for glioblastomas (106.98 (S.D. 43.82) versus 33.08 (S.D. 21.55) ng/ml, p = 0.004). Western blotting showed that in the meningioma group, the molecular weight pattern was constant with a dominant well-defined band at 41 kD. Peritumoural tissue demonstrated two bands, with the stronger band at 41 kD and a slightly weaker band at 71 kD. In the glioblastoma group, there was more heterogeneity, with a dominant 41 kD band found in all tumour and peritumoural samples, together with additional bands at 34, 58 and 66 kD. Conclusion: These results indicate that (1) tPA is present in larger quantities in glioblastoma compared to meningioma and normal brain, (2) tPA quantity is not significantly different in the peritumoural tissue adjacent to glioblastoma but is significantly less for meningioma, and (3) tPA is expressed in more heterogenous forms in glioblastoma. This present study therefore suggests that the expression of tPA in a brain tumour may be an additional prognostic factor in terms of its malignant and invasive potential.

Principes du traitement des sarcomes des tissus mous de l'adulte

Improving the quality of life of patients with a soft tissue sarcoma necessitates first the initiation of a first-line carcinologic treatment aimed at reducing the risk of local recurrence and reiterated surgeries likely to lead to mutilation; second, it necessitates a functional surgery which is increasingly feasible since the implementation of adequate multidisciplinary therapeutic management by a specialized team. No surgery should be undertaken without prior adapted imaging. Performing preoperating biopsy following the MRI allows a straightaway definition of the therapeutic management. Decision making should be based on definitive histological result since extemporaneous examination is associated with a high risk of error. Carcinologic surgery consists on a large exeresis with histologically healthy resection margins. A priori amputation is an outdated management, first of all because in this procedure the margins are not always healthy. The surgical access follows the member axis orientation. The biopsy scar, the tumour, and a round margin of non-tumoural tissue (a 2-cm depth of muscle, or a fibrous anatomical barrier such an aponeurosis) must be removed all together in order to avoid the occurrence of tumoural break-in and spreading. Advances in reconstructive surgery allow attenuating the functional consequences of a wide exeresis. The good quality of the surgery is determined by the histological analysis of the margins, i.e., the amount of peritumoural healthy tissue. Surgical re-intervention should be discussed in case of unhealthy margins because radiotherapy does not correct non-adapted surgery. In the standard procedure, radiotherapy is associated to carcinologic surgery. However, according to retrospective studies, the carcinologic surgical exeresis of some low-grade, superficially localized, small tumours may be sufficient, but this remains to be validated by prospective studies. Chemotherapy is discussed in young patients whose sarcoma is of high-grade malignancy. Finally, the technique of the isolated limb perfusion, using extra-corporeal circulation, allows perfusing high doses of chemotherapy, and improves the carcinologic and functional result of the second-line surgery undertaken for some recurrent tumours or locally advanced tumours. The organization and realization of such therapies is a matter for specialized multidisciplinary teams.

Papillary carcinoma of the thyroid: evidence for a role for hepatocyte growth factor (HGF) in promoting tumour angiogenesis.

The pattern of vascularization of papillary carcinoma was investigated in tumour sections from 31 cases and in primary cultures from 12 cases. Tumour sections were immunostained for von Willebrand Factor (vWF) to visualize blood vessels; for endothelial-specific nitric-oxide-synthase (EC-NOS), as a marker of endothelial cell activation; and for Ki-67 to evaluate endothelial cell proliferation. It was found that endothelial cells lining venous vessels located in peritumoural fibrous tissue were intensely EC-NOS-positive and occasionally Ki-67-positive. Capillary vessels of tumour papillae were not stained for Ki-67 and were weakly EC-NOS-positive. Primary cultures of papillary carcinoma cells were used as a potential source of factors active on endothelial cells. It was found that thyroid tumour cells contain RNAs for angiopoietin, vascular endothelial growth factor (VEGF), and VEGF-C; moreover, they release large amounts of VEGF into culture supernatants and exert chemotactic activity in vitro for the endothelial cell line SIEC. The ability of papillary carcinoma cells to release angiogenic factors could be stimulated in vitro. Hepatocyte growth factor (HGF; 25 ng/ml) induced a 1.2- to 5-fold increase in the amount of VEGF released by tumour cells and a 1.2- to 4.2-fold increase in the amount of chemotactic activity present in culture supernatants. Met protein, the high affinity HGF-receptor, is overexpressed in a large proportion of cases of papillary carcinoma. These findings are consistent with the possibility that HGF-Met protein interaction is one of the molecular mechanisms promoting the vascularization of papillary carcinoma of the thyroid.

Baseline levels of glucose metabolites, glutamate and glycerol in malignant glioma assessed by stereotactic microdialysis.

The metabolism of high grade astrocytoma was studied in 15 patients using intra-tumoural microdialysis. Two catheters were implanted during a stereotactic biopsy procedure: one in the tumour and one in the peri-tumoural tissue. The patients were fully mobilized the same day as the operation. Microdialysis samples were collected the next day and subsequently analysed for glucose, lactate, pyruvate, glutamate and glycerol. The main objective was to establish base-line levels of the studied substances. In addition, an in vitro experiment was performed in order to estimate recovery for the flow rates and catheters used. Glucose showed a tendency to be lower in tumour than in peri-tumoural tissue, indicating a high energy demand of the tumour. Lactate was significantly higher in tumour tissue. This supports previous reports that high grade astrocytomas use glycolysis rather than respiration to meet their energy demand. The tumours were also classified into necrotic and non-necrotic, according to the radiological finding. The necrotic tumours showed significantly higher levels of glutamate. They also presented a tendency to higher levels of glycerol than the non-necrotic tumours. These findings might be explained by the release of intracellular glutamate and of cell-membrane glycerol by cell destruction. We believe that microdialysis in awake and mobilized patients will prove to be a valuable tool in investigating metabolic events in malignant brain tumours especially during therapy.

Locoregional radioimmunotherapy in selected patients with malignant glioma: experiences, side effects and survival times.

Prognosis of malignant glioma is very unfavourable mainly due to minimal tumour remnants in the peritumoural tissue. Intralesionally applied radioimmunotherapy is a possible therapeutical option with the potential to improve survival of patients with malignant glioma. We investigated side effects and survival after surgery, conventional radiotherapy and additional radioimmunotherapy with labelled tenascin-antibodies in patients with malignant glioma. Since 1995, 37 patients were treated with radioimmunotherapy after resection and radiotherapy of a malignant glioma. Patients received antibodies labelled with yttrium-90 and iodine-131 in different doses into the tumour cavity via a previously implanted ommaya-reservoir. Treatment was applied in up to 8 cycles (mean 2.96 cycles) in time intervals of 6-8 weeks. Mean age was 46 years, histology was anaplastic astrocytoma in 13 patients and glioblastoma in 24 patients. For the whole group median survival time has not yet been reached. For glioblastoma the median survival time is 17 months, 5-year survival probability for anaplastic astrocytoma is 85% approximately. Quality of life was acceptable. Acute side effects following treatment were headache, seizures and worsening of pre-existing neurological symptoms. Late side effects were skin necrosis and, in 1 case, a delayed aphasia probably due to a vascular lesion. Radioimmunotherapy prolonged survival time in a selected group of patients with malignant gliomas as compared to a historical control group. Patients with anaplastic astrocytomas seem to have more benefit from this therapy than patients with glioblastomas.

Intralesional radioimmunotherapy in the treatment of malignant glioma: clinical and experimental findings.

In the last two decades radioimmunotherapy has been used as an additional treatment option for malignant glioma in several centers. More than 400 patients have been reported, who were treated in the framework of different studies. Most of them received labelled antibodies to tenascin, an extracellular matrix-glycoprotein, which is expressed in high amounts in malignant gliomas. We report side effects and survival time of 46 patients, treated after surgical resection and conventional radiotherapy with intralesionally injected labelled (131-Iodine) antibodies to tenascin. Despite the fact, that many treatments have been performed, little is known about the distribution properties of labelled antibodies after injection in the tumour cavity. For an optimal effect labelled antibodies should be able to reach tumour cells, which have migrated into the surrounding tissue. We investigated the propagation velocity and area of distribution of labelled antibodies and their considerably smaller fragments after the injection in C6-gliomas of Wistar rats. Propagation increased with time and was significantly greater after injection of labelled fragments than after injection of labelled antibodies. According to our results labelled fragments might be better able to reach distant tumour cells in the peritumoural tissue of malignant gliomas than labelled antibodies.

Strategies for MMP inhibition in cancer: innovations for the post-trial era

For more than two decades, the view that tumour-associated matrix metalloproteinases (MMPs) were required for peritumour tissue degradation and metastasis dominated the drive to develop MMP inhibitors as anticancer therapeutics. Until recently, clinical trials with MMP inhibitors have yielded disappointing results, highlighting the need for better insight into the mechanisms by which this growing family of multifunctional enzymes contribute to tumour growth. It is now recognized that MMP activity is tightly regulated at several levels, providing new avenues for blocking these enzymes. What are the different approaches that can be used to target MMPs, and which of these might lead to new therapeutic strategies for cancer?

Vascularization of cutaneous melanoma involves vessel co-option and has clinical significance.

This study was undertaken to determine the role and the fate of the peritumoural vascular plexus during the vascularization of human malignant melanoma (hMM) and in an appropriate murine melanoma model system. The prognostic significance of the vascularity of different tumour areas was also evaluated. Despite morphometry revealing several-fold higher microvessel densities (MVDs) in the peritumoural tissue than at the centre of the tumour, the development of visceral metastases of hMM was exclusively correlated with the MVD of the tumour centre. Furthermore, the 5-year survival of the patient group with low tumour centre MVD (<30/mm(2), n=29) was 100%, compared to 1/16 patients alive with high tumour centre MVD (>30/mm(2), n=16). Morphometric analysis and three-dimensional reconstruction of vessel networks of both human and murine melanomas showed clearly that the peritumoural vascular plexus present at the melanoma base is continuously being incorporated into the growing tumour mass. Once vessels become incorporated, sprouting ceases and the proliferating endothelial cells (EC) take part only in vessel dilatation. Moreover, the immunohistochemical and ultrastructural characterization of microvessels demonstrated that the pericyte coverage of endothelial tubes was complete in all of the investigated areas, in both human and murine melanomas.

Experimental research photodynamic effects in perifocal, oedematous brain tissue.

Photodynamic therapy (PDT) has been under discussion as additional treatment option for malignant gliomas. However, damage not only to tumour tissue but also to normal brain has been demonstrated. The mechanisms of this unwanted side effect have not yet been clearly identified. Spreading of photosensitiser with oedema after disruption of the blood-brain-barrier and potential sensitisation of normal tissue has been found previously. The present study investigates the time- and dose-dependency of normal tissue damage to photodynamic therapy using Photofrin II after disruption of the blood-brain-barrier. Male wistar rats anaesthetised with chloral hydrate were subjected to focal, cerebral cold lesions. Simultaneously, Photofrin II (PFII) was injected (2,5 or 5 mg/kg b.w.). Laser irradiation (630 nm) was performed after 4 h, 12 h and 24 h with varying light doses. Control groups were subjected to focal cold lesion alone, cold lesion with laser irradiation, PFII followed by laser irradiation, or laser irradiation alone (n=6 all groups). 24 h later, brains were removed for assessment of necrosis in coronal sections. Light dose had a significant impact on the extent of necrosis. Compared to control animals (lesion only: 0.84 +/- 0.2 mm2; lesion and irradiation alone: 0.7 +/- 0.3 mm2), the area of necrosis was increased to 2.8 +/- 0.5 (50 J/cm2), 3.5 +/- 1,1 (100 J/cm2) and 4.3 +/- 0.7 mm2 (200 J/cm2, 5 mg/kg b.w.; p<0.01). This effect was time-dependent. Maximal necrosis (6.3 +/- 1,6 mm2) was observed when brains were irradiated 12 h after PFII injection, with less necrosis occurring at 24 h (2.8 +/- 0.4 mm2, p<0.01). Reducing sensitiser dose to 2.5 mg/kg b.w. resulted in a reduction of necrosis (2.09 +/- 0.2 mm2, p<0.05). Damage to oedematous tissue after photodynamic therapy using i.v. PFII and laser light at 630 nm depends on laser dose, sensitiser dose and the time point of laser irradiation. The time point of PDT should be considered to prevent unwanted tissue reactions. In the clinical setting however, defined damage to peritumoural tissue may be advantageous. This should be achievable by optimised timing and dosage of photodynamic therapy.

Nitric oxide synthase and cytochrome c oxidase changes in the tumoural and peritumoural cerebral cortex.

We analysed changes in nitric oxide synthase (NOS) and cytochrome oxidase (CO) activities in the tumoural and peritumoural cerebral cortex in order to investigate: a) the role of NO in tumourigenesis, in TBF regulation, and in vasogenetic PBE; b) the metabolic changes caused by the neoplasm in the surrounding tissues. Intra-operative samples of cerebral cortex were studied by means of immunohistochemistry for nNOS and iNOS, and by histochemistry for NADPH-diaphorase (NADPH-d) and CO. In contrast with normal cortex, reactive glial cells and the endothelium of small blood vessels displayed strong NADPH-d and iNOS activities in oedematous peritumoural tissue. In the tumoural cortex, NADPH-d and nNOS-positive neurones were reduced in number and their dendrites were thin and interrupted, and infiltrates of NADPH-d and iNOS-positive tumoural cells were frequent. CO activity was decreased in the deep layers of peritumoural cortex, and it was almost absent in the tumoural cortex. In peritumoural and tumoural cortex changes in NOS and CO activities suggest that the coupling between neuronal activity and blood flow is impaired in the damaged cerebral cortex, and that the increase in NOS activity may play a role in tumour vascularization and progression.

Targeting of liver tumour in rats by selective delivery of holmium-166 loaded microspheres: a biodistribution study

Intra-arterial administration of beta-emitting particles that become trapped in the vascular bed of a tumour and remain there while delivering high doses, represents a unique approach in the treatment of both primary and metastatic liver tumours. Studies on selective internal radiation therapy of colorectal liver metastases using yttrium-90 glass microspheres have shown encouraging results. This study describes the biodistribution of 40-microm poly lactic acid microspheres loaded with radioactive holmium-166, after intra-arterial administration into the hepatic artery of rats with implanted liver tumours. Radioactivity measurements showed >95% retention of injected activity in the liver and its resident tumour. The average activity detected in other tissues was < or =0.1%ID/g, with incidental exceptions in the lungs and stomach. Very little 166Ho activity was detected in kidneys (<0.1%ID/g), thereby indicating the stability of the microspheres in vivo. Tumour targeting was very effective, with a mean tumour to liver ratio of 6. 1+/-2.9 for rats with tumour (n=15) versus 0.7+/-0.5 for control rats (n=6; P<0.001). These ratios were not significantly affected by the use of adrenaline. Histological analysis showed that five times as many large (>10) and medium-sized (4-9) clusters of microspheres were present within tumour and peritumoural tissue, compared with normal liver. Single microspheres were equally dispersed throughout the tumour, as well as normal liver parenchyma.

Polarographic measurements of oxygen tension in human glioma and surrounding peritumoural brain tissue

This study quantifies the spatial distribution of pO 2 in glioma and in the surrounding brain tissue. Both glioma and peritumoural brain contain regions at oxygen tensions less than 2.5 mmHg. Modalities targeting hypoxia to improve the efficacy of therapy may have an important role in the management of this disease.

Platinum distribution in malignant glioma following intraoperative intravenous infusion of carboplatin

The objective of this paper was to determine the time course and extent of platinum uptake into human malignant glioma tissue. An intraoperative, intravenous infusion of carboplatin was given to nine patients (seven glioblastoma and two anaplastic glioma) undergoing tumour excision. Carboplatin dosage was calculated individually to achieve a target systemic free carboplatin exposure.Tumour and peritumoural tissue was harvested at timed intervals following carboplatin administration. Plasma and tumour platinum concentrations were measured by graphite furnace flameless atomic absorption spectrophotometry. Histological examination was also performed on a piece of each tissue sample. The mean carboplatin dose administered was 783, SEM. 56 mg (range 485-903). Plasma pharmacokinetics showed a typical elimination curve. The mean peak plasma platinum concentration was 44, SEM 5 mug/ml (range 27-74).The mean total elemental plasma platinum area under the curve (AUC) was 9.0, SEM 1.4 mg/ml/min. Platinum was detected in 61 tumour samples, the mean peak concentration being 13 SEM 2 mug/g (range 5-21). Platinum was also detected in peritumoural brain and necrotic tumour. No correlation was apparent between the degree of necrosis in each tumour specimen and tumour platinum concentration. Platinum concentrations achieved in tumour were similar to levels that would be cytotoxic for glioma cells in vitro. The results of this study have implications for future studies using capillary permeability modifying agents as adjuncts to brain tumour chemotherapy.

Liposome-delivered 131I-labelled Zn(II)-phthalocyanine as a radiodiagnostic agent for tumours.

131I-Zn(II)-phthalocyanine (ZnPc) incorporated into unilamellar liposomes has been systemically injected to mice bearing a transplanted MS-2 fibrosarcoma. Biodistribution studies show that the pharmacokinetic behaviour of 131I-ZnPc is very similar to that defined for the parent molecule ZnPc including a serum half-life of ca. 12 h, a high recovery from liver and spleen and minimal accumulation in kidney and brain. The most important pharmacokinetic parameter is represented by the high tumour/ muscle ratio of 131I-ZnPc concentration (ca. 9 at 24 h post-injection). These results suggest the possible use of the radiolabelled derivative for a real-time non-invasive monitoring of the ZnPc concentration in the tumour and peritumoural tissue during photodynamic therapy.

Tumour photosensitizers: approaches to enhance the selectivity and efficiency of photodynamic therapy

While Photofrin, the photosensitizer currently in clinical use for photodynamic therapy (PDT) of tumours, has been shown to be both efficacious and safe in the treatment of a variety of human cancers, its chemical heterogeneity and low absorbance in the phototherapeutically useful wavelength range (600–850 nm) make the development of new photosensitizers with improved characteristics desirable. A suitable manipulation of the molecular structure of porphyrins offers several interesting possibilities for controlling the optical and photophysical oroperties of the photosensitizer, as well as its biodistribution between tomour and peritumoural tissues or at the subtissular and subcellular level. The achievement of these goals may also be facilitated by the association of the photosensitizer with selected delivery systems, opening the way to a qualitative and quantitative improvement of PDT.

Differential expression of adenosine A1 receptors in colorectal cancer and related mucosa.

Adenosine A1 receptors (A1R) are known to inhibit while the A2 receptors (A2R) stimulate the G-protein cAMP second messenger system and may play a role in cell growth and carcinogenesis. Using a quantitative reverse transcription-polymerase chain reaction (RT-PCR) method, mRNA for A1R and A2R was measured in human colorectal adenocarcinomas and individual peritumoural colon tissues. There was differential expression of the mRNA for A1R with tumour tissues having significantly higher amounts compared to peritumoural normal tissues. The mRNA for A2R was not found to be differentially expressed. The increase in the inhibitory A1 receptor in tumour tissues may be in response to increased adenosine release from the hypoxic cells found in malignant tumour tissues, thus indicating a possible role for the adenosine A1 receptor in carcinogenesis.

Factors Involved In the Plasminogen Activation System in Human Breast Tumours

The plasminogen activation system is a delicately balanced assembly of enzymes which seems to have primary influence on tumour progression. The conversion of plasminogen into serine protease plasmin with fibrinolytic activity depends on the actual balance between plasminogen activators (urokinase type; u-PA and tissue type; t-PA) and their inhibitors (type 1 and 2 plasminogen activator inhibitors; PAI-1 and PAI-2). The purpose of this study was to determine the exact histological localization of all the major factors involved in plasminogen activation, and activation inhibition (plasmin system) in benign and malignant breast tumour samples. Our results show that factors of the plasmin system are present both in benign and malignant tumours. Cancer cells strongly labelled for both u-PA and t-PA, but epithelial cells of fibroadenoma samples were also stained for plasminogen activators at least as intensively as tumour cells in cancerous tissues. In fibroadenomas, all the epithelial cells were labelled for PAI-1. Staining became sporadic in malignant tumours, cells located at the periphery of tumour cell clusters regularly did not show reaction for PAI-1. In the benign tumour samples the perialveolar connective tissue stroma contained a lot of PAI-1 positive cells, showing characteristics of fibroblasts; but their number was strongly decreased in the stroma of malignant tumours. These findings indicate that the higher level of u-PA antigen, detected in malignant breast tumour samples by biochemical techniques, does not necessarily indicate increased u-PA production by tumour cells but it might be owing to the increased number of cells producing u-PA as well.(ABSTRACT TRUNCATED AT 250 WORDS)

In situ detection of transforming growth factor-β mRNA in experimental rat glioma and reactive glial cells

Malignant gliomas are associated with a state of systemic immunosuppression which appears to be partially mediated by transforming growth factor beta (TGF-β) secreted from glioma cells. In a recently described animal model of malignant glioma, massive activation of local microglial cells and formation of microglia-derived macrophages has been observed in the absence of detectable tumour regression. We have investigated the in situ expression of TGF-β in rat glioma as a possible cause of ineffective tumour destruction. Two weeks following unilateral injection of glioma cells, large tumours were observed in the affected hemisphere. In situ hybridization for TGF-β1 mRNA revealed an intense signal over the entire tumour area. In the peritumoural area, at sites of glial activation, a lower signal was obtained over cellular profiles containing nuclei typical for microglia, as well as other unidentified cellular profiles. No signal was obtained over the contralateral unaffected hemisphere. Northern blot analysis revealed a strong expression of TGF-β1 mRNA in tumour tissue, a lesser signal in the peritumoural reactive brain tissue and virtually no signal in normal tissue. Our data indicate that the experimental rat glioma has the potential to secrete TGF-β in vivo which might render the microglial infiltration ineffective. TGF-β expressed by activated microglial cells themselves might further inhibit their tumoricidal potential, thus contributing further to unrestrained tumour growth.

Determination of endogenous serum proteins in normal and oedematous brain tissue of cat by rocket and crossed immunoelectrophoresis

A quantitative method for determination of endogenous serum proteins has been established and tested in an experimental model of peritumoural brain oedema in cats. Rocket and crossed immunoelectrophoresis were applied for determination of total serum proteins, albumin, IgG and haemoglobin in blood and brain homogenates. Modifications such as the use of non-ionic detergents and of antisera with different specificity were established for each antigen under investigation. The content of total serum proteins, albumin and IgG was substantially higher in tumour and peritumoural brain tissue than in the non-oedematous brain. The measurement of haemoglobin allowed the calculation of blood volume and, in consequence, the differentiation between intra- and extravascular serum proteins. The results are in line with earlier measurements obtained by different analytical methods and demonstrate that the present technique provides a reliable approach for the quantitative assessment of serum protein extravasation.

Tetra- n-propylporphycene as a tumour localizer: pharmacokinetic and phototherapeutic studies in mice

The porphin isomer tetra-n-propyl-porphycene (TPP) was incorporated into unilamellar liposomes of dipalmitoylphosphatidylcholine and intravenously injected at a dose of 2 mg/kg to BALB c mice bearing a MS-2 fibrosarcoma. Pharmacokinetic studies show that TPP is selectively transported by serum lipoproteins and delivered to the tumour tissue with good efficiency (approx. 1 μg of the TPP per g of tissue at 24 h after injection) and selectivity (ratio of TPP concentration in the tumour to the peritumoural tissue 16.7 at 24 h). Large doses of TPP are also accumulated by the liver, in agreement with the elimination of the drug via the biliary route, while no TPP is recovered from the brain. Red light-irradiation (300 J/cm 2) of the tumour area caused extensive necrosis, while only little cutaneous photosensitivity was observed. Since TPP has a large absorbance in the 630–640 nm region, can be synthesized with a high degree of purity and is an efficient generator of singlet oxygen, this drug represents a potential candidate as a phototherapeutic agent for tumours.