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. 1996 Feb;73(4):514–521. doi: 10.1038/bjc.1996.89

Evaluation of porphyrin C analogues for photodynamic therapy of cerebral glioma.

G Karagianis 1, J S Hill 1, S S Stylli 1, A H Kaye 1, N J Varadaxis 1, J A Reiss 1, D R Phillips 1
PMCID: PMC2074451  PMID: 8595167

Abstract

A series of monomeric porphyrins (2-8) based on porphyrin C (1) have been tested as sensitisers for photodynamic therapy (PDT) of cerebral glioma using the in vitro/in vivo C6 intracerebral animal tumour model. The in vivo screening, consisting of cytotoxicity, phototoxicity (red light) and subcellular localisation studies, revealed two sensitisers (porphyrin 7, molecular weight 863 Da and porphyrin 8, molecular weight 889 Da), which had greater photoactivity than porphyrin C and similar photoactivity to haematoporphyrin derivative (HpD) although at a 5-fold higher dose than HpD. Both sensitisers showed intracellular localisation to discrete organelle sites and exhibited considerably less 'dark' cytotoxicity than HpD. The kinetics of uptake of porphyrins 7 and 8 was studied in the mouse C6 glioma model as well as in biopsy samples from normal brain, liver, spleen and blood. Maximal drug uptake levels in tumour occurred 9 and 6 h after intraperitoneal injection for 7 and 8 respectively, at which time the tumour to normal brain ratios were 15:1 and 13:1 respectively. The effect of PDT using porphyrin 7 activated by the gold metal vapour laser tuned to 627.8 nm was studied in Wistar rats bearing intracerebral C6 glioma. At a drug dose of 10 mg porphyrin 7 kg-1 body weight and laser doses of up to 400 J cm-2 light, selective tumour kill with sparing of normal brain was achieved, with a maximal depth of tumour kill of 1.77+/-0.40. mm. Irradiation following a higher drug dose of 75 mg porphyrin 7 kg-1 body weight resulted in a greater depth of tumour kill, but also significantly increased the likelihood and extent of necrosis in normal brain.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Dougherty T. J. Photosensitizers: therapy and detection of malignant tumors. Photochem Photobiol. 1987 Jun;45(6):879–889. doi: 10.1111/j.1751-1097.1987.tb07898.x. [DOI] [PubMed] [Google Scholar]
  2. Gomer C. J. Photodynamic therapy in the treatment of malignancies. Semin Hematol. 1989 Jan;26(1):27–34. [PubMed] [Google Scholar]
  3. Hill J. S., Kahl S. B., Kaye A. H., Stylli S. S., Koo M. S., Gonzales M. F., Vardaxis N. J., Johnson C. I. Selective tumor uptake of a boronated porphyrin in an animal model of cerebral glioma. Proc Natl Acad Sci U S A. 1992 Mar 1;89(5):1785–1789. doi: 10.1073/pnas.89.5.1785. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Hill J. S., Kaye A. H., Sawyer W. H., Morstyn G., Megison P. D., Stylli S. S. Selective uptake of hematoporphyrin derivative into human cerebral glioma. Neurosurgery. 1990 Feb;26(2):248–254. doi: 10.1097/00006123-199002000-00011. [DOI] [PubMed] [Google Scholar]
  5. Kaye A. H., Morstyn G., Ashcroft R. G. Uptake and retention of hematoporphyrin derivative in an in vivo/in vitro model of cerebral glioma. Neurosurgery. 1985 Dec;17(6):883–890. doi: 10.1227/00006123-198512000-00002. [DOI] [PubMed] [Google Scholar]
  6. Kaye A. H., Morstyn G., Gardner I., Pyke K. Development of a xenograft glioma model in mouse brain. Cancer Res. 1986 Mar;46(3):1367–1373. [PubMed] [Google Scholar]
  7. Kaye A. H., Morstyn G. Photoradiation therapy causing selective tumor kill in a rat glioma model. Neurosurgery. 1987 Mar;20(3):408–415. doi: 10.1227/00006123-198703000-00009. [DOI] [PubMed] [Google Scholar]
  8. Kessel D., Cheng M. L. Biological and biophysical properties of the tumor-localizing component of hematoporphyrin derivative. Cancer Res. 1985 Jul;45(7):3053–3057. [PMC free article] [PubMed] [Google Scholar]
  9. MacRobert A. J., Bown S. G., Phillips D. What are the ideal photoproperties for a sensitizer? Ciba Found Symp. 1989;146:4–16. doi: 10.1002/9780470513842.ch2. [DOI] [PubMed] [Google Scholar]
  10. Schneckenburger H., Rück A., Bartos B., Steiner R. Intracellular distribution of photosensitizing porphyrins measured by video-enhanced fluorescence microscopy. J Photochem Photobiol B. 1988 Nov;2(3):355–363. doi: 10.1016/1011-1344(88)85054-1. [DOI] [PubMed] [Google Scholar]
  11. Verma A., Nye J. S., Snyder S. H. Porphyrins are endogenous ligands for the mitochondrial (peripheral-type) benzodiazepine receptor. Proc Natl Acad Sci U S A. 1987 Apr;84(8):2256–2260. doi: 10.1073/pnas.84.8.2256. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Woodburn K. W., Vardaxis N. J., Hill J. S., Kaye A. H., Phillips D. R. Subcellular localization of porphyrins using confocal laser scanning microscopy. Photochem Photobiol. 1991 Nov;54(5):725–732. doi: 10.1111/j.1751-1097.1991.tb02081.x. [DOI] [PubMed] [Google Scholar]
  13. Yamada K., Ushio Y., Hayakawa T., Kato A., Yamada N., Mogami H. Quantitative autoradiographic measurements of blood-brain barrier permeability in the rat glioma model. J Neurosurg. 1982 Sep;57(3):394–398. doi: 10.3171/jns.1982.57.3.0394. [DOI] [PubMed] [Google Scholar]

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