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. 1987 Apr;55(4):389–395. doi: 10.1038/bjc.1987.78

Photodynamic therapy with phthalocyanine sensitisation: quantitative studies in a transplantable rat fibrosarcoma.

C J Tralau, A J MacRobert, P D Coleridge-Smith, H Barr, S G Bown
PMCID: PMC2001712  PMID: 3580264

Abstract

Photodynamic therapy (PDT) is a promising approach to the local destruction of malignant tumours, but little work has been done to determine which factors control the extent of tissue necrosis produced. Using a new photosensitiser, a sulphonated aluminium phthalocyanine (AlSPc) and light from an argon ion pumped dye laser at 675 nm, we quantified the effects of interstitial PDT in a transplantable fibrosarcoma in rats. At 100mW laser power, thermal effects were comparable to those of PDT, so subsequent studies were carried out at 50 mW, where thermal effects were minimal. The depth of PDT necrosis increased with the logarithm of the applied energy. Tissue concentration of AlSPc was measured by alkali extraction and at all times after sensitisation, correlated well with the necrosis produced with a given light dose. Peak tumour concentration of AlSPc occurred 24-48 h after sensitisation compared with a peak at 3 h in muscle. The peak ratio tumour:muscle was 2:1 at 24 h. Apart from a different time interval to reach the peak sensitiser concentration, the extent of tumour damage varied with the light and sensitiser parameters in a similar way to that found in normal liver, although the optical penetration depth was greater in the tumour (2.5 mm vs. 1.8 mm). At doses of AlSPc below 1 mg kg-1 the diameter of necrosis increased with the logarithm of the dose of sensitiser, and doubling the dose from 0.25 to 0.5 mg kg-1 increased the depth of necrosis by 50%. However, at higher doses, the changes were smaller and increasing the dose from 2.5 to 5 mg kg-1 only increased the necrosis by 10% for the same light dose. In all dose ranges, a given percentage increase in the tissue concentration of AlSPc gave a much smaller percentage increase in the extent of necrosis for the same light dose, suggesting that selectivity of necrosis between tumour and normal tissue is likely to be much less than the selectivity of retention of the photosensitiser. From these results, the extent of PDT necrosis in this fibrosarcoma is as predictable as it is in normal liver if the light dose, tissue concentration of AlSPc and optical penetration depth of the tissue are known. Further studies are now required on different tumour models to establish how tumours respond compared with adjacent normal tissue when the tumour is growing in its organ of origin rather than the non-physiological situation using a transplantable tumour as in this study.

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Selected References

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  1. Agrez M. V., Wharen R. E., Jr, Anderson R. E., Laws E. R., Jr, Ilstrup D. M., Cortese D. A., Shorter R. G., Lieber M. M. Hematoporphyrin derivative: quantitative uptake in dimethylhydrazine-induced murine colorectal carcinoma. J Surg Oncol. 1983 Nov;24(3):173–176. doi: 10.1002/jso.2930240305. [DOI] [PubMed] [Google Scholar]
  2. Ben-Hur E., Rosenthal I. Photosensitized inactivation of Chinese hamster cells by phthalocyanines. Photochem Photobiol. 1985 Aug;42(2):129–133. doi: 10.1111/j.1751-1097.1985.tb01550.x. [DOI] [PubMed] [Google Scholar]
  3. Bown S. G., Tralau C. J., Smith P. D., Akdemir D., Wieman T. J. Photodynamic therapy with porphyrin and phthalocyanine sensitisation: quantitative studies in normal rat liver. Br J Cancer. 1986 Jul;54(1):43–52. doi: 10.1038/bjc.1986.150. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Bugelski P. J., Porter C. W., Dougherty T. J. Autoradiographic distribution of hematoporphyrin derivative in normal and tumor tissue of the mouse. Cancer Res. 1981 Nov;41(11 Pt 1):4606–4612. [PubMed] [Google Scholar]
  5. Chan W. S., Svensen R., Phillips D., Hart I. R. Cell uptake, distribution and response to aluminium chloro sulphonated phthalocyanine, a potential anti-tumour photosensitizer. Br J Cancer. 1986 Feb;53(2):255–263. doi: 10.1038/bjc.1986.43. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Gomer C. J., Dougherty T. J. Determination of [3H]- and [14C]hematoporphyrin derivative distribution in malignant and normal tissue. Cancer Res. 1979 Jan;39(1):146–151. [PubMed] [Google Scholar]
  7. Gregorie H. B., Jr, Horger E. O., Ward J. L., Green J. F., Richards T., Robertson H. C., Jr, Stevenson T. B. Hematoporphyrin-derivative fluorescence in malignant neoplasms. Ann Surg. 1968 Jun;167(6):820–828. doi: 10.1097/00000658-196806000-00002. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Jori G., Beltramini M., Reddi E., Salvato B., Pagnan A., Ziron L., Tomio L., Tsanov T. Evidence for a major role of plasma lipoproteins as hematoporphyrin carriers in vivo. Cancer Lett. 1984 Oct;24(3):291–297. doi: 10.1016/0304-3835(84)90025-9. [DOI] [PubMed] [Google Scholar]
  9. Jori G., Reddi E., Cozzani I., Tomio L. Controlled targeting of different subcellular sites by porphyrins in tumour-bearing mice. Br J Cancer. 1986 May;53(5):615–621. doi: 10.1038/bjc.1986.104. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. LIPSON R. L., BALDES E. J., OLSEN A. M. The use of a derivative of hematoporhyrin in tumor detection. J Natl Cancer Inst. 1961 Jan;26:1–11. [PubMed] [Google Scholar]
  11. Mew D., Wat C. K., Towers G. H., Levy J. G. Photoimmunotherapy: treatment of animal tumors with tumor-specific monoclonal antibody-hematoporphyrin conjugates. J Immunol. 1983 Mar;130(3):1473–1477. [PubMed] [Google Scholar]
  12. Profio A. E., Doiron D. R. Dosimetry considerations in phototherapy. Med Phys. 1981 Mar-Apr;8(2):190–196. doi: 10.1118/1.594932. [DOI] [PubMed] [Google Scholar]
  13. Rousseau J., Ali H., Lamoureux G., Lebel E., van Lier J. E. Synthesis, tissue distribution and tumor uptake of 99mTc- and 67Ga-tetrasulfophthalocyanine. Int J Appl Radiat Isot. 1985 Sep;36(9):709–716. doi: 10.1016/0020-708x(85)90041-9. [DOI] [PubMed] [Google Scholar]
  14. Rousseau J., Autenrieth D., van Lier J. E. Synthesis, tissue distribution and tumor uptake of [99Tc]tetrasulfophthalocyanine. Int J Appl Radiat Isot. 1983 Mar;34(3):571–579. doi: 10.1016/0020-708x(83)90058-3. [DOI] [PubMed] [Google Scholar]
  15. Spikes J. D. Phthalocyanines as photosensitizers in biological systems and for the photodynamic therapy of tumors. Photochem Photobiol. 1986 Jun;43(6):691–699. doi: 10.1111/j.1751-1097.1986.tb05648.x. [DOI] [PubMed] [Google Scholar]
  16. Svaasand L. O., Ellingsen R. Optical properties of human brain. Photochem Photobiol. 1983 Sep;38(3):293–299. doi: 10.1111/j.1751-1097.1983.tb02674.x. [DOI] [PubMed] [Google Scholar]
  17. Weishaupt K. R., Gomer C. J., Dougherty T. J. Identification of singlet oxygen as the cytotoxic agent in photoinactivation of a murine tumor. Cancer Res. 1976 Jul;36(7 Pt 1):2326–2329. [PubMed] [Google Scholar]
  18. el-Far M. A., Pimstone N. R. The interaction of tumour-localizing porphyrins with collagen, elastin, gelatin, fibrin and fibrinogen. Cell Biochem Funct. 1985 Apr;3(2):115–119. doi: 10.1002/cbf.290030206. [DOI] [PubMed] [Google Scholar]
  19. van Lier J. E., Ali H., Rousseau J. Phthalocyanines labeled with gamma-emitting radionuclides as possible tumor scanning agents. Prog Clin Biol Res. 1984;170:315–319. [PubMed] [Google Scholar]

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