Chlorin and Porphyrin Derivatives as Potential Photosensitizers in Photodynamic Therapy

Pandey, Ravindra K.; Bellnier, David A.; Smith, Kevin M.; Dougherty, Thomas J.

doi:10.1111/j.1751-1097.1991.tb08468.x

Cited by 169 publications

(95 citation statements)

References 28 publications

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“…Intraoperative PDT of a tumour bed following surgery is a promising concept for tumours not removable with the required margins of tumour-free tissue. Pilot studies have been done in this respect with HpD and DHE for retroperitoneal sarcomas (Nambisan et al, 1987), residual or recurrent colorectal cancer in the pelvis (Herrera-Ornelas et al, 1985), diffuse malignant mesothelioma (Pass et al, 1990;Lofgren et al, 1991) and for disseminated intraperitoneal malignancies (Sindelar et al, 1991). The results of these studies indicate that large surface PDT is feasible: however, the tumouricidal effect for intraoperative large surface PDT has not been proven in these reports.…”

Section: Discussionmentioning

confidence: 90%

“…Both depend on the sensitiser used and, according to the given sensitiser, on the interplay of its dose, the light dose and the time interval between application and activation. To overcome the shortcomings of HpD and DHE, new sensitisers have been developed with improved properties in this respect (Pandey et al, 1991). Among chlorins, mTHPC has shown excellent tumour eradication and tissue selectivity in rodents, requiring only 10 Joules cm-2 to induce tumour necrosis of 0.6 cm depth, and without apparent side effects and minimal skin sensitivity (Berenbaum et al, 1989).…”

Section: Discussionmentioning

confidence: 99%

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Photodynamic therapy with chlorins for diffuse malignant mesothelioma: initial clinical results

Ris

Altermatt²,

Inderbitzi³

et al. 1991

Br J Cancer

210

117

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Summary Four patients underwent intraoperative photodynamic therapy after surgery with meso-tetra-(hydroxyphenyl)-chlorin (mTHPC-PDT) for diffuse malignant mesothelioma. Preliminary procedures were performed in two patients in order to establish the efficacy of mTHPC-PDT and to optimise its tumoricidal effect. The (Faber, 1988). Improved local control does require additional measures, but the disease responds poorly to radio-and chemotherapy (Lerner et al., 1983). As photodynamic therapy (PDT) has been reported to be effective in human mesothelioma xenografts (Feins et al., 1990), it might allow for an appropriate 'clean-up' of the thoracic cavity after surgery. For clinical purposes, the currently used sensitisers for PDT are haematoporphyrin derivatives (HpD) and dihaematoporphyrin ether (DHE) . However, PDT with meso-tetra-(hydroxyphenyl)-chlorin (mTHPC) was superior to DHE-PDT with respect to antitumour activity and tissue selectivity in rodents without causing significant toxicity (Berenbaum, 1989). mTHPC might therefore be better fitted to large surface PDT as required for diffuse malignant mesothelioma treatment. A pilot study was done to evaluate mTHPC-PDT for diffuse malignant mesothelioma with respect to its antitumour activity and the feasibility of a combined modality approach under clinical conditions. Patients and methodsFour patients underwent mTHPC-PDT for diffuse malignant mesothelioma. Each patient was informed in detail about the experimental nature of the procedure and consent was obtained from each patient and from the local Human Investigations Committee of our institution.The four men were aged 46 (patient 1), 48 (patient 2), 65 (patient 3) and 50 years (patient 4), all having had possible occupation related exposure to asbestos. The main symptoms at admission were dyspnoea due to pleural effusion, chest pain and loss of weight. There was no evidence of disease in the peritoneal and contralateral chest cavity on CT-scans at admission. The right side was involved in patients 1, 2 and 4 and the left in patient 3. Previous biopsies revealed an epithelial (Figure la), a biphasic (Figure 2a), a sarcomatous and a mixed type of mesothelioma in the four patients and was confirmed in every case by immunohistologic examinations.Preliminary PDT To establish the efficacy of mTHPC-PDT and to optimise its tumouricidal effect, preliminary PDT was performed in patients 1 and 2 prior to its definitive application. Modulations of mTHPC dose, light dose and of the time interval between mTHPC application and activation were tested. mTHPC (Scotia Pharmaceuticals Ltd, Guildford, UK) was dissolved in 20% ethanol, 30% polyethylene glycol 400 and 50% H20 and administered over 15 min i.v. through a bacterial filter under sterile conditions within 60 min of preparation. Argon-pumped dye laser light of 650 nm (Coherent Innova 200 and Dye CR 599, GMP SA, Lausanne, Switzerland) was delivered through a sterilised optical fibre on tumour areas of 3 cm diameter. The power at the end of the optical fibre was measured wi...

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Section: Discussionmentioning

confidence: 90%

Section: Discussionmentioning

confidence: 99%

Photodynamic therapy with chlorins for diffuse malignant mesothelioma: initial clinical results

Ris

Altermatt²,

Inderbitzi³

et al. 1991

Br J Cancer

210

117

View full text Add to dashboard Cite

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“…However, prolonged skin photosensitivity due to non-specific localisation of the photosensitiser is associated with Photofrinmediated PDT (Benson, 1988). Therefore new photosensitisers and better methods of photosensitiser localisation are being investigated (Bachor et al, 1991;Goff et al, 1991;Gomer, 1991;Pandey et al, 1991;Hasan, 1992;Henderson & Dougherty, 1992). Other approaches for achieving better localisation include local administration of the photosensitiser (Amano et al, 1988;Bachor et al, 1992).…”

mentioning

confidence: 99%

A mechanistic study of cellular photodestruction with 5-aminolaevulinic acid-induced porphyrin

Iinuma

Farshi²,

Ortel³

et al. 1994

Br J Cancer

236

120

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“…A previous study showed that the passage of hypericin into the circulatory system is minimal, with undetectable levels in plasma or serum (45). Retention of hypericin in the skin guarantees a treatment that targets the affected area, thus avoiding possible systemic toxic effects, as happens with other drugs used for the treatment of CL or even with other photosensitizers used to treat other diseases (46,47).…”

Section: Discussionmentioning

confidence: 99%

Development of a Novel Formulation with Hypericin To Treat Cutaneous Leishmaniasis Based on Photodynamic Therapy inIn VitroandIn VivoStudies

Montoya

Daza

Muñoz

et al. 2015

Antimicrob Agents Chemother

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An evaluation of the leishmanicidal activity in vitro and in vivo of hypericin, an expanded-spectrum photosensitizer found in Hypericum perforatum, is presented. Hypericin was evaluated against intracellular amastigotes in vitro of Leishmania (Viannia) panamensis. A topical formulation containing 0.5% hypericin was developed and assayed in vivo in a hamster model of cutaneous leishmaniasis. Results demonstrate that hypericin induces a significant antiamastigote effect in vitro against L. panamensis by decreasing the number of parasites inside infected cells. The topical formulation of 0.5% hypericin allows healing of L. panamensis-induced lesions upon a topical application of 40 mg/day plus visible-light irradiation (5 J/cm 2 , 15 min), twice a week for 3 weeks. Cutaneous leishmaniasis (CL) is a parasitic disease caused by protozoa of the genus Leishmania, which manifests as a chronic infection affecting mainly mononuclear phagocytes of the skin (1). The disease affects the poorest populations in 99 countries in tropical and subtropical regions of the world (2, 3). It is estimated that 14 million people are infected, 350 million are at risk, and there are about 1.5 million new cases per year (3, 4). The parasite is transmitted by the bite of an insect vector belonging to the genus Lutzomyia (in America) or Phlebotomus (in Europe, Asia, and Africa) in the subfamily Phlebotominae (5).Only three types of drugs are available to treat CL. They are the pentavalent antimonials (meglumine antimoniate and sodium stibogluconate), pentamidine isethionate, and miltefosine. Miltefosine is the only one available for oral administration (4). These medications are delivered at high doses and for long periods, thus leading to high toxicity. Therefore, their use is contraindicated in pregnant women, in patients with cardiovascular, renal, or hepatic disease, and in children with low body weight (6). Overall, the efficacy of these drugs varies between 55 and 98% depending on the compound and on the Leishmania species causing the clinical manifestation (7,8). However, their elevated toxicity encourages abandonment of treatment and consequently a decrease in the efficacy (9).More recently, photodynamic therapy (PDT) has emerged as an alternative to treat CL (10). This therapy is based on the application of a photosensitizing agent (PA) that, when excited by light of a certain wavelength, induces the production of reactive oxygen species (ROS) that can destroy the microorganism or the target cell (11). In spite of its potential, only a few PAs have been tested against CL in animal models, and only one in humans. Topical application of 5-aminolevulinic acid (ALA) and light in a murine model of CL caused by L. major showed a significant reduction of the parasitic load and the size of lesions (12). Intralesional administration of ALA (one to three PDT sessions) in a patient with CL by L. major produced a 10 to 20% cure, although it is probable that clinical outcome resulted from nonspecific destruction of infected macrophages instead of...

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Chlorin and Porphyrin Derivatives as Potential Photosensitizers in Photodynamic Therapy

Cited by 169 publications

References 28 publications

Photodynamic therapy with chlorins for diffuse malignant mesothelioma: initial clinical results

Photodynamic therapy with chlorins for diffuse malignant mesothelioma: initial clinical results

A mechanistic study of cellular photodestruction with 5-aminolaevulinic acid-induced porphyrin

Development of a Novel Formulation with Hypericin To Treat Cutaneous Leishmaniasis Based on Photodynamic Therapy inIn VitroandIn VivoStudies

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