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British Journal of Cancer logoLink to British Journal of Cancer
. 1995 Nov;72(5):1113–1119. doi: 10.1038/bjc.1995.473

The effect of aminolaevulinic acid-induced, protoporphyrin IX-mediated photodynamic therapy on the cremaster muscle microcirculation in vivo.

J Leveckis 1, N J Brown 1, M W Reed 1
PMCID: PMC2033946  PMID: 7577455

Abstract

The effect of photodynamic therapy on normal striated muscle was investigated using 30 adult male rats. Animals were divided into six groups. Three control groups received phosphate-buffered saline by gavage and violet light at 105, 178 and 300 mW cm-2 respectively. Three experimental groups received aminolaevulinic acid (ALA; 200 mg kg-1) and violet light at 105, 178 and 300 mW cm-2 respectively. After exposure of the cremaster muscle animals were allowed to equilibrate and vessel diameters and bloodflow assessed. Following photoactivation measurements were taken every 10 min over a 2 h period. Photoactivation of experimental groups at the two higher power densities resulted in an initial decrease in both arteriolar and venular diameters, and a concomitant decrease in blood flow. The magnitude of these changes and the degree of recovery by the end of the observation period was related to power density. No effects were observed in the control groups. These results suggest that microcirculatory damage may contribute to the mechanism of action of photodynamic therapy with ALA.

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Selected References

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  1. BERLIN N. I., NEUBERGER A., SCOTT J. J. The metabolism of delta -aminolaevulic acid. 1. Normal pathways, studied with the aid of 15N. Biochem J. 1956 Sep;64(1):80–90. doi: 10.1042/bj0640080. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. BERLIN N. I., NEUBERGER A., SCOTT J. J. The metabolism of delta -aminolaevulic acid. 2. Normal pathways, studied with the aid of 14C. Biochem J. 1956 Sep;64(1):90–100. doi: 10.1042/bj0640090. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Baez S. An open cremaster muscle preparation for the study of blood vessels by in vivo microscopy. Microvasc Res. 1973 May;5(3):384–394. doi: 10.1016/0026-2862(73)90054-x. [DOI] [PubMed] [Google Scholar]
  4. Balchum O. J., Doiron D. R., Huth G. C. Photoradiation therapy of endobronchial lung cancers employing the photodynamic action of hematoporphyrin derivative. Lasers Surg Med. 1984;4(1):13–30. doi: 10.1002/lsm.1900040104. [DOI] [PubMed] [Google Scholar]
  5. Bedwell J., MacRobert A. J., Phillips D., Bown S. G. Fluorescence distribution and photodynamic effect of ALA-induced PP IX in the DMH rat colonic tumour model. Br J Cancer. 1992 Jun;65(6):818–824. doi: 10.1038/bjc.1992.175. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. CASTELLANI A., PACE G. P., CONCIOLI M. Photodynamic effect of haematoporphyrin on blood microcirculation. J Pathol Bacteriol. 1963 Jul;86:99–102. doi: 10.1002/path.1700860111. [DOI] [PubMed] [Google Scholar]
  7. Chatlani P. T., Nuutinen P. J., Toda N., Barr H., MacRobert A. J., Bedwell J., Bown S. G. Selective necrosis in hamster pancreatic tumours using photodynamic therapy with phthalocyanine photosensitization. Br J Surg. 1992 Aug;79(8):786–790. doi: 10.1002/bjs.1800790826. [DOI] [PubMed] [Google Scholar]
  8. Chaudhuri K., Keck R. W., Selman S. H. Morphological changes of tumor microvasculature following hematoporphyrin derivative sensitized photodynamic therapy. Photochem Photobiol. 1987 Nov;46(5):823–827. doi: 10.1111/j.1751-1097.1987.tb04854.x. [DOI] [PubMed] [Google Scholar]
  9. Divaris D. X., Kennedy J. C., Pottier R. H. Phototoxic damage to sebaceous glands and hair follicles of mice after systemic administration of 5-aminolevulinic acid correlates with localized protoporphyrin IX fluorescence. Am J Pathol. 1990 Apr;136(4):891–897. [PMC free article] [PubMed] [Google Scholar]
  10. 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]
  11. Fingar V. H., Wieman T. J., Doak K. W. Role of thromboxane and prostacyclin release on photodynamic therapy-induced tumor destruction. Cancer Res. 1990 May 1;50(9):2599–2603. [PubMed] [Google Scholar]
  12. Fingar V. H., Wieman T. J., Wiehle S. A., Cerrito P. B. The role of microvascular damage in photodynamic therapy: the effect of treatment on vessel constriction, permeability, and leukocyte adhesion. Cancer Res. 1992 Sep 15;52(18):4914–4921. [PubMed] [Google Scholar]
  13. Harty J. I., Amin M., Wieman T. J., Tseng M. T., Ackerman D., Broghamer W. Complications of whole bladder dihematoporphyrin ether photodynamic therapy. J Urol. 1989 Jun;141(6):1341–1346. doi: 10.1016/s0022-5347(17)41302-4. [DOI] [PubMed] [Google Scholar]
  14. Henderson B. W., Waldow S. M., Mang T. S., Potter W. R., Malone P. B., Dougherty T. J. Tumor destruction and kinetics of tumor cell death in two experimental mouse tumors following photodynamic therapy. Cancer Res. 1985 Feb;45(2):572–576. [PubMed] [Google Scholar]
  15. Kennedy J. C., Pottier R. H. Endogenous protoporphyrin IX, a clinically useful photosensitizer for photodynamic therapy. J Photochem Photobiol B. 1992 Jul 30;14(4):275–292. doi: 10.1016/1011-1344(92)85108-7. [DOI] [PubMed] [Google Scholar]
  16. 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]
  17. Leveckis J., Burn J. L., Brown N. J., Reed M. W. Kinetics of endogenous protoporphyrin IX induction by aminolevulinic acid: preliminary studies in the bladder. J Urol. 1994 Aug;152(2 Pt 1):550–553. doi: 10.1016/s0022-5347(17)32791-x. [DOI] [PubMed] [Google Scholar]
  18. Loh C. S., Bedwell J., MacRobert A. J., Krasner N., Phillips D., Bown S. G. Photodynamic therapy of the normal rat stomach: a comparative study between di-sulphonated aluminium phthalocyanine and 5-aminolaevulinic acid. Br J Cancer. 1992 Sep;66(3):452–462. doi: 10.1038/bjc.1992.295. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Loh C. S., MacRobert A. J., Bedwell J., Regula J., Krasner N., Bown S. G. Oral versus intravenous administration of 5-aminolaevulinic acid for photodynamic therapy. Br J Cancer. 1993 Jul;68(1):41–51. doi: 10.1038/bjc.1993.284. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Meininger G. A., Fehr K. L., Yates M. B. Anatomic and hemodynamic characteristics of the blood vessels feeding the cremaster skeletal muscle in the rat. Microvasc Res. 1987 Jan;33(1):81–97. doi: 10.1016/0026-2862(87)90009-4. [DOI] [PubMed] [Google Scholar]
  21. Nseyo U. O. Photodynamic therapy. Urol Clin North Am. 1992 Aug;19(3):591–599. [PubMed] [Google Scholar]
  22. Pope A. J., MacRobert A. J., Phillips D., Bown S. G. The detection of phthalocyanine fluorescence in normal rat bladder wall using sensitive digital imaging microscopy. Br J Cancer. 1991 Nov;64(5):875–879. doi: 10.1038/bjc.1991.417. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Pottier R. H., Chow Y. F., LaPlante J. P., Truscott T. G., Kennedy J. C., Beiner L. A. Non-invasive technique for obtaining fluorescence excitation and emission spectra in vivo. Photochem Photobiol. 1986 Nov;44(5):679–687. doi: 10.1111/j.1751-1097.1986.tb04726.x. [DOI] [PubMed] [Google Scholar]
  24. Reed M. W., Miller F. N., Wieman T. J., Tseng M. T., Pietsch C. G. The effect of photodynamic therapy on the microcirculation. J Surg Res. 1988 Nov;45(5):452–459. doi: 10.1016/0022-4804(88)90195-3. [DOI] [PubMed] [Google Scholar]
  25. Reed M. W., Schuschke D. A., Ackermann D. M., Harty J. I., Wieman T. J., Miller F. N. The response of the rat urinary bladder microcirculation to photodynamic therapy. J Urol. 1989 Sep;142(3):865–868. doi: 10.1016/s0022-5347(17)38932-2. [DOI] [PubMed] [Google Scholar]
  26. Reed M. W., Schuschke D. A., Miller F. N. Prostanoid antagonists inhibit the response of the microcirculation to "early" photodynamic therapy. Radiat Res. 1991 Sep;127(3):292–296. [PubMed] [Google Scholar]
  27. Reed M. W., Wieman T. J., Doak K. W., Pietsch C. G., Schuschke D. A. The microvascular effects of photodynamic therapy: evidence for a possible role of cyclooxygenase products. Photochem Photobiol. 1989 Sep;50(3):419–423. doi: 10.1111/j.1751-1097.1989.tb04179.x. [DOI] [PubMed] [Google Scholar]
  28. Reed M. W., Wieman T. J., Schuschke D. A., Tseng M. T., Miller F. N. A comparison of the effects of photodynamic therapy on normal and tumor blood vessels in the rat microcirculation. Radiat Res. 1989 Sep;119(3):542–552. [PubMed] [Google Scholar]
  29. Selman S. H., Kreimer-Birnbaum M., Chaudhuri K., Garbo G. M., Seaman D. A., Keck R. W., Ben-Hur E., Rosenthal I. Photodynamic treatment of transplantable bladder tumors in rodents after pretreatment with chloroaluminum tetrasulfophthalocyanine. J Urol. 1986 Jul;136(1):141–145. doi: 10.1016/s0022-5347(17)44759-8. [DOI] [PubMed] [Google Scholar]
  30. Selman S. H., Kreimer-Birnbaum M., Goldblatt P. J., Anderson T. S., Keck R. W., Britton S. L. Jejunal blood flow after exposure to light in rats injected with hematoporphyrin derivative. Cancer Res. 1985 Dec;45(12 Pt 1):6425–6427. [PubMed] [Google Scholar]
  31. Selman S. H., Kreimer-Birnbaum M., Klaunig J. E., Goldblatt P. J., Keck R. W., Britton S. L. Blood flow in transplantable bladder tumors treated with hematoporphyrin derivative and light. Cancer Res. 1984 May;44(5):1924–1927. [PubMed] [Google Scholar]
  32. Selman S. H., Milligan A. J., Kreimer-Birnbaum M., Keck R. W., Goldblatt P. J., Britton S. L. Hematoporphyrin derivative photochemotherapy of experimental bladder tumors. J Urol. 1985 Feb;133(2):330–333. doi: 10.1016/s0022-5347(17)48933-6. [DOI] [PubMed] [Google Scholar]
  33. Shulok J. R., Klaunig J. E., Selman S. H., Schafer P. J., Goldblatt P. J. Cellular effects of hematoporphyrin derivative photodynamic therapy on normal and neoplastic rat bladder cells. Am J Pathol. 1986 Feb;122(2):277–283. [PMC free article] [PubMed] [Google Scholar]
  34. Star W. M., Marijnissen H. P., van den Berg-Blok A. E., Versteeg J. A., Franken K. A., Reinhold H. S. Destruction of rat mammary tumor and normal tissue microcirculation by hematoporphyrin derivative photoradiation observed in vivo in sandwich observation chambers. Cancer Res. 1986 May;46(5):2532–2540. [PubMed] [Google Scholar]
  35. Tseng M. T., Reed M. W., Ackermann D. M., Schuschke D. A., Wieman T. J., Miller F. N. Photodynamic therapy induced ultrastructural alterations in microvasculature of the rat cremaster muscle. Photochem Photobiol. 1988 Nov;48(5):675–681. doi: 10.1111/j.1751-1097.1988.tb02880.x. [DOI] [PubMed] [Google Scholar]
  36. Tseng M. T., Schuschke D. A., Reed M. W., Harty J. I., Wieman T. J., Fingar V. H. The influence of photodynamic therapy on the ultrastructure of the normal rat bladder. J Photochem Photobiol B. 1991 Jun;9(3-4):295–305. doi: 10.1016/1011-1344(91)80167-g. [DOI] [PubMed] [Google Scholar]
  37. Wieman T. J., Mang T. S., Fingar V. H., Hill T. G., Reed M. W., Corey T. S., Nguyen V. Q., Render E. R., Jr Effect of photodynamic therapy on blood flow in normal and tumor vessels. Surgery. 1988 Sep;104(3):512–517. [PubMed] [Google Scholar]
  38. Wolf P., Rieger E., Kerl H. Topical photodynamic therapy with endogenous porphyrins after application of 5-aminolevulinic acid. An alternative treatment modality for solar keratoses, superficial squamous cell carcinomas, and basal cell carcinomas? J Am Acad Dermatol. 1993 Jan;28(1):17–21. doi: 10.1016/0190-9622(93)70002-b. [DOI] [PubMed] [Google Scholar]
  39. van der Veen N., van Leengoed H. L., Star W. M. In vivo fluorescence kinetics and photodynamic therapy using 5-aminolaevulinic acid-induced porphyrin: increased damage after multiple irradiations. Br J Cancer. 1994 Nov;70(5):867–872. doi: 10.1038/bjc.1994.412. [DOI] [PMC free article] [PubMed] [Google Scholar]

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