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. 1994 Oct;70(4):604–610. doi: 10.1038/bjc.1994.358

Cellular levels of photosensitisers in tumours: the role of proximity to the blood supply.

M Korbelik 1, G Krosl 1
PMCID: PMC2033422  PMID: 7917904

Abstract

Flow cytometry using the tumour perfusion probe Hoechst 33342 was employed to examine the distribution of photosensitisers in tumour cells located at different distances from the blood supply. Two tumour models, the SCCVII squamous cell carcinoma and FsaR fibrosarcoma growing in C3H/HeN mice, were used in the experiments. Among the photosensitisers tested, only BPD (benzoporphyrin derivative monoacid) exhibited uniform distribution in tumour cells irrespective of their distance from the vasculature. In this respect, 5-aminolaevulinic acid (i.e. its metabolite protoporphyrin IX), di- and tetrasulphonated aluminium phthalocyanines (A1PcS2 and AlPcS4), di- and tetrasulphonated tetraphenylporphines (TPPS2 and TPPS4), Photofrin and bacteriochlorophyll-a (i.e. its metabolite bacteriopheophytin-a) followed BPD in decreasing order in their efficacy of accumulation in tumour cells remote from the blood supply. This photosensitiser property appeared not to depend on tumour type, tumour size, route of photosensitiser administration, time after the administration, photosensitiser lipophilicity or on the presence of host cell infiltrate in the tumour. Following treatment with photodynamic therapy (PDT) in vivo, tumour cells were sorted based on their blood vessel proximity and their survival was determined by colony formation assay. The data demonstrate that the direct killing of tumour cells by Photofrin- and A1PcS2-based PDT decreases with increasing distance of the cells from the blood supply.

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Selected References

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  1. Bellnier D. A., Ho Y. K., Pandey R. K., Missert J. R., Dougherty T. J. Distribution and elimination of Photofrin II in mice. Photochem Photobiol. 1989 Aug;50(2):221–228. doi: 10.1111/j.1751-1097.1989.tb04152.x. [DOI] [PubMed] [Google Scholar]
  2. Chaplin D. J., Durand R. E., Olive P. L. Cell selection from a murine tumour using the fluorescent probe Hoechst 33342. Br J Cancer. 1985 Apr;51(4):569–572. doi: 10.1038/bjc.1985.79. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Chaplin D. J., Olive P. L., Durand R. E. Intermittent blood flow in a murine tumor: radiobiological effects. Cancer Res. 1987 Jan 15;47(2):597–601. [PubMed] [Google Scholar]
  4. Durand R. E., Chaplin D. J., Olive P. L. Cell sorting with Hoechst or carbocyanine dyes as perfusion probes in spheroids and tumors. Methods Cell Biol. 1990;33:509–518. doi: 10.1016/s0091-679x(08)60550-6. [DOI] [PubMed] [Google Scholar]
  5. Henderson B. W., Fingar V. H. Oxygen limitation of direct tumor cell kill during photodynamic treatment of a murine tumor model. Photochem Photobiol. 1989 Mar;49(3):299–304. doi: 10.1111/j.1751-1097.1989.tb04110.x. [DOI] [PubMed] [Google Scholar]
  6. Henderson B. W., Sumlin A. B., Owczarczak B. L., Dougherty T. J. Bacteriochlorophyll-a as photosensitizer for photodynamic treatment of transplantable murine tumors. J Photochem Photobiol B. 1991 Sep;10(4):303–313. doi: 10.1016/1011-1344(91)80016-b. [DOI] [PubMed] [Google Scholar]
  7. Kennedy J. C., Pottier R. H., Pross D. C. Photodynamic therapy with endogenous protoporphyrin IX: basic principles and present clinical experience. J Photochem Photobiol B. 1990 Jun;6(1-2):143–148. doi: 10.1016/1011-1344(90)85083-9. [DOI] [PubMed] [Google Scholar]
  8. Kessel D. Porphyrin-lipoprotein association as a factor in porphyrin localization. Cancer Lett. 1986 Nov;33(2):183–188. doi: 10.1016/0304-3835(86)90023-6. [DOI] [PubMed] [Google Scholar]
  9. Korbelik M. Distribution of disulfonated and tetrasulfonated aluminum phthalocyanine between malignant and host cell populations of a murine fibrosarcoma. J Photochem Photobiol B. 1993 Oct;20(2-3):173–181. doi: 10.1016/1011-1344(93)80148-3. [DOI] [PubMed] [Google Scholar]
  10. Korbelik M., Krosl G., Olive P. L., Chaplin D. J. Distribution of Photofrin between tumour cells and tumour associated macrophages. Br J Cancer. 1991 Sep;64(3):508–512. doi: 10.1038/bjc.1991.339. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Olive P. L., Chaplin D. J., Durand R. E. Pharmacokinetics, binding and distribution of Hoechst 33342 in spheroids and murine tumours. Br J Cancer. 1985 Nov;52(5):739–746. doi: 10.1038/bjc.1985.252. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Olive P. L. Distribution, oxygenation, and clonogenicity of macrophages in a murine tumor. Cancer Commun. 1989;1(2):93–100. doi: 10.3727/095535489820875273. [DOI] [PubMed] [Google Scholar]
  13. Pass H. I. Photodynamic therapy in oncology: mechanisms and clinical use. J Natl Cancer Inst. 1993 Mar 17;85(6):443–456. doi: 10.1093/jnci/85.6.443. [DOI] [PubMed] [Google Scholar]
  14. Peng Q., Moan J., Farrants G., Danielsen H. E., Rimington C. Localization of potent photosensitizers in human tumor LOX by means of laser scanning microscopy. Cancer Lett. 1990 Sep;53(2-3):129–139. doi: 10.1016/0304-3835(90)90205-c. [DOI] [PubMed] [Google Scholar]

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