Abstract
The selectivities of Photofrin II (Ph II) and four new photosensitizers for tumour and normal tissues have been compared by cost-benefit analysis. Mice were given tetra(p-hydroxyphenyl)porphyrin (p-THPP) or tetra(m-hydroxyphenyl)porphyrin (m-THPP) or the corresponding chlorins (p-THPC, m-THPC, respectively) or Ph II. Twenty-four hours later, tumour (PC6) or normal skin, muscle and bladder were illuminated with 10 J cm−2 light from a dye laser at the appropriate wavelengths. Damage indices were (i) depth of tumour necrosis, (ii) oedema measured by increase in weight of skin, muscle and bladder, (iii) extravasation of systemically administered Evans blue into skin and bladder and (iv) muscle necrosis. Dose-response curves were constructed and selectivities compared by determining the level of benefit (depth of tumour necrosis) obtained for specific costs (damage to normal tissue). m-THPC was by far the most selective for tumour compared with normal tissues and Ph II the least. For example, for a cost in oedema that doubled skin weight, the depth of tumour necrosis was 1.1 mm for Ph II, 3 mm for p-THPP, 4.1 mm for m-THPP, 5.6 mm for p-THPC, and 6.3 mm for m-THPC. m-THPC appears to be a promising sensitizer for clinical investigation.
The cost-benefit analysis method addresses the problem of comparing different types of damage. It removes from consideration the individual dose-response curves, and relates benefit (damage to tumour) to cost (damage to normal tissue) for a range of photosensitizers. The method is considered to have wide applicability in drug evaluation (where in the more general case the benefit may relate to an improvement which is not damage-mediated). In clinical medicine, the method is seen to offer a useful way of making progress even in those cases where costs and benefits are a matter of judgement rather than quantification.
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References
Dougherty TJ. Photosensitisers: therapy and detection of malignant tumours.Photochem Photobiol 1987,45:879–89
Wan S, Parrish JA, Anderson RR et al. Transmittance of non-ionising radiation in human tissues.Photochem. Photobiol 1981,34:679–81
Berenbaum MC, Akande SL, Bonnett R et al.Meso-Tetra(hydroxyphenyl)porphyrins, a new class of potent tumour photosensitisers with favourable selectivity.Br J Cancer 1986,54:717
Chevretton EB. The effect of photodynamic therapy on normal skeletal muscle and intramuscular tumour in an animal model. MS Thesis, University of London, 1989
Chevretton EB, Berenbaum MC, Bonnett R. The effect of photodynamic therapy on normal skeletal muscle in an animal model.Lasers Med Sci 1992,7:103–10
Plail RO. Studies on the histological effects of photodynamic therapy in normal and neoplastic rat bladder and investigation of light distribution within the human bladder. MS Thesis, University of London, 1990
Dougherty TJ.Photosensitizing Compounds: Their Chemistry, Biology and Clinical Use. Bock G, Harnett S (eds)Ciba Foundation Symp 1989,146:53
Berenbaum MC, Bonnett R. Tetra(hydroxyphenyl)porphyrins. In: Kessel D (ed)Photodynamic Therapy of Neoplastic Disease, Vol 2. Boca Raton: CRC Press, 1990:169–77
Selman SH, Garbo GM, Kelk RW et al. A dose response analysis of porphyrin derivatives used as sensitisers for photodynamic treatment of transplantable urothelial tumours.J Urol 1987,137:1255–7
Kessel D, Smith K. Photosensitisation with derivatives of chlorophyll.Photochem Photobiol 1989,49:157–60
Bonnett R, Berenbaum MC. Porphyrins as photosensitisers. In:Photosensitizing Compounds: Their Chemistry, Biology and Clinical Use. Bock G, Harnett S (eds)Ciba Foundation Symp, 1989,146:33–59
Ali H, Langlois R, Wagner JR et al. Biological activities of phthalocyanines. X. Synthesis and analysis of sulphonated phonated phthalocyanines.Photochem Photobiol 1988,47:713–7
Barr H, Tralau CJ, Boulos PB et al. Selective necrosis in dimethylhydrazine-induced rat colon tumours using phthalocyanine photodynamic therapy.Gastroenterology 1990,98:1532–7
Bonnett R, White RD, Winfield U-J et al. Hydroporphyrins of themeso-tetra(hydroxyphenyl)porphyrin series as tumour photosensitisers.Biochem J 1989,261:277–80
Bonnett R, Ioannou S, White RD et al.Meso-tetra(hydroxyphenyl)porphyrins as tumour photosensitisers: chemical and photochemical aspects.Photobiochem Photobiophys 1987 (Suppl):45–56
Berenbaum MC, Bonnett R, Scourides PA. In vivo biological activity of the components of haematoporphyrin derivative.Br J Cancer 1982,45:571
Green CJ.Animal Anaesthesia. London: Laboratory Animals Ltd, 1979:80
Harada A, Takeuchi M, Fukao T et al. A simple method for the quantitative extraction of dye extravasated into the skin.J Pharm Pharmacol 1970,23:218–9
Jenkins CE. A decalcifying and dehydrating fixative.J. Pathol Bacteriol 1921,24:166
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Berenbaum, M.C., Bonnett, R., Chevretton, E.B. et al. Selectivity ofmeso-tetra(hydroxyphenyl)porphyrins and chlorins and of photofrin II in causing photodamage in tumour, skin, muscle and bladder. The comcept of cost-benefit in analysing the results. Laser Med Sci 8, 235–243 (1993). https://doi.org/10.1007/BF02547845
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DOI: https://doi.org/10.1007/BF02547845