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British Journal of Cancer logoLink to British Journal of Cancer
. 2001 Jan 1;84(1):33–37. doi: 10.1054/bjoc.2000.1532

Photodynamic diagnosis of breast tumours after oral application of aminolevulinic acid

D P Ladner 1,2, R A Steiner 1, J Allemann 3, U Haller 2, H Walt 2
PMCID: PMC2363621  PMID: 11139309

Abstract

Photodynamic diagnosis is of increasing interest for diagnosis in oncology. It is based on a more intense incorporation of a fluorescent dye in tumours compared to normal tissue. As a feasibility study we investigated the effectiveness of oral application of 5-aminolevulinic acid for photodynamic diagnosis of human primary mammary tumours. The study included 16 patients with palpable breast tumours. Aminolevulinic acid was administered at a concentration of 40 mg kg−1bodyweight 150–420 min prior to tumourectomy. Intraoperatively blue light (405 nm) was applied to the operation site. Sections of the excised tumour and some lymph nodes were prepared and analysed with a fluorescent microscope. All primary mammary tumour tissues showed significantly higher fluorescence intensity than surrounding normal mammary tissue. Fluorescence of the mammary tumours could also be discriminated macroscopically and intraoperatively. Fluorescence intensity in nonmetastatic lymph node tissue was higher in 2 out of 3 patients than in primary tumour tissue. By photodynamic diagnosis using aminolevulinic acid we were able to reliably distinguish primary mammary tumours from normal mammary tissue microscopically and macroscopically in all our patients. We suggest that photodynamic diagnosis with aminolevulinic acid for breast tumours should be further investigated and developed for intraoperative use and may well be a simple tool for better intraoperative diagnosis and recognition of tumour margins. We hypothesize that lymph node metastasis of breast tumours will not be detectable by this method. © 2001 Cancer Research Campaign http://www.bjcancer.com

Keywords: aminolevulinic acid, photosensitizer, photodynamic diagnosis, photodynamic therapy, breast tumours, axillary lymph nodes

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Selected References

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  1. Campbell D. L., Gudgin-Dickson E. F., Forkert P. G., Pottier R. H., Kennedy J. C. Detection of early stages of carcinogenesis in adenomas of murine lung by 5-aminolevulinic acid-induced protoporphyrin IX fluorescence. Photochem Photobiol. 1996 Oct;64(4):676–682. doi: 10.1111/j.1751-1097.1996.tb03123.x. [DOI] [PubMed] [Google Scholar]
  2. Dougherty T. J., Marcus S. L. Photodynamic therapy. Eur J Cancer. 1992;28A(10):1734–1742. doi: 10.1016/0959-8049(92)90080-l. [DOI] [PubMed] [Google Scholar]
  3. Eléouet S., Carré J., Vonarx V., Heyman D., Lajat Y., Patrice T. Delta-aminolevulinic acid-induced fluorescence in normal human lymphocytes. J Photochem Photobiol B. 1997 Nov;41(1-2):22–29. doi: 10.1016/s1011-1344(97)00063-8. [DOI] [PubMed] [Google Scholar]
  4. Fehr M. K., Chapman C. F., Krasieva T., Tromberg B. J., McCullough J. L., Berns M. W., Tadir Y. Selective photosensitizer distribution in vulvar condyloma acuminatum after topical application of 5-aminolevulinic acid. Am J Obstet Gynecol. 1996 Mar;174(3):951–957. doi: 10.1016/s0002-9378(96)70332-0. [DOI] [PubMed] [Google Scholar]
  5. Gannon M. J., Johnson N., Roberts D. J., Holroyd J. A., Vernon D. I., Brown S. B., Lilford R. J. Photosensitization of the endometrium with topical 5-aminolevulinic acid. Am J Obstet Gynecol. 1995 Dec;173(6):1826–1828. doi: 10.1016/0002-9378(95)90435-2. [DOI] [PubMed] [Google Scholar]
  6. Gibson S. L., Havens J. J., Foster T. H., Hilf R. Time-dependent intracellular accumulation of delta-aminolevulinic acid, induction of porphyrin synthesis and subsequent phototoxicity. Photochem Photobiol. 1997 Mar;65(3):416–421. doi: 10.1111/j.1751-1097.1997.tb08580.x. [DOI] [PubMed] [Google Scholar]
  7. Henderson B. W., Dougherty T. J. How does photodynamic therapy work? Photochem Photobiol. 1992 Jan;55(1):145–157. doi: 10.1111/j.1751-1097.1992.tb04222.x. [DOI] [PubMed] [Google Scholar]
  8. Heyerdahl H., Wang I., Liu D. L., Berg R., Andersson-Engels S., Peng Q., Moan J., Svanberg S., Svanberg K. Pharmacokinetic studies on 5-aminolevulinic acid-induced protoporphyrin IX accumulation in tumours and normal tissues. Cancer Lett. 1997 Jan 30;112(2):225–231. doi: 10.1016/s0304-3835(96)04576-4. [DOI] [PubMed] [Google Scholar]
  9. Hua Z., Gibson S. L., Foster T. H., Hilf R. Effectiveness of delta-aminolevulinic acid-induced protoporphyrin as a photosensitizer for photodynamic therapy in vivo. Cancer Res. 1995 Apr 15;55(8):1723–1731. [PubMed] [Google Scholar]
  10. Kato H., Aizawa K., Ono J., Konaka C., Kawate N., Yoneyama K., Kinoshita K., Nishimiya K., Sakai H., Noguchi M. Clinical measurement of tumor fluorescence using a new diagnostic system with hematoporphyrin derivative, laser photoradiation, and a spectroscope. Lasers Surg Med. 1984;4(1):49–58. doi: 10.1002/lsm.1900040107. [DOI] [PubMed] [Google Scholar]
  11. 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]
  12. 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]
  13. Khan S. A., Dougherty T. J., Mang T. S. An evaluation of photodynamic therapy in the management of cutaneous metastases of breast cancer. Eur J Cancer. 1993;29A(12):1686–1690. doi: 10.1016/0959-8049(93)90105-o. [DOI] [PubMed] [Google Scholar]
  14. Krammer B., Uberriegler K. In-vitro investigation of ALA-induced protoporphyrin IX. J Photochem Photobiol B. 1996 Nov;36(2):121–126. doi: 10.1016/s1011-1344(96)07358-7. [DOI] [PubMed] [Google Scholar]
  15. Kriegmair M., Baumgartner R., Knuechel R., Steinbach P., Ehsan A., Lumper W., Hofstädter F., Hofstetter A. Fluorescence photodetection of neoplastic urothelial lesions following intravesical instillation of 5-aminolevulinic acid. Urology. 1994 Dec;44(6):836–841. doi: 10.1016/s0090-4295(94)80167-3. [DOI] [PubMed] [Google Scholar]
  16. Leunig A., Rick K., Stepp H., Gutmann R., Alwin G., Baumgartner R., Feyh J. Fluorescence imaging and spectroscopy of 5-aminolevulinic acid induced protoporphyrin IX for the detection of neoplastic lesions in the oral cavity. Am J Surg. 1996 Dec;172(6):674–677. doi: 10.1016/s0002-9610(96)00312-1. [DOI] [PubMed] [Google Scholar]
  17. 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]
  18. Marcus S. L., Sobel R. S., Golub A. L., Carroll R. L., Lundahl S., Shulman D. G. Photodynamic therapy (PDT) and photodiagnosis (PD) using endogenous photosensitization induced by 5-aminolevulinic acid (ALA): current clinical and development status. J Clin Laser Med Surg. 1996 Apr;14(2):59–66. doi: 10.1089/clm.1996.14.59. [DOI] [PubMed] [Google Scholar]
  19. Navone N. M., Polo C. F., Frisardi A. L., Andrade N. E., Battle A. M. Heme biosynthesis in human breast cancer--mimetic "in vitro" studies and some heme enzymic activity levels. Int J Biochem. 1990;22(12):1407–1411. doi: 10.1016/0020-711x(90)90230-z. [DOI] [PubMed] [Google Scholar]
  20. Obwegeser A., Jakober R., Kostron H. Uptake and kinetics of 14C-labelled meta-tetrahydroxyphenylchlorin and 5-aminolaevulinic acid in the C6 rat glioma model. Br J Cancer. 1998 Sep;78(6):733–738. doi: 10.1038/bjc.1998.569. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Peng Q., Moan J., Warloe T., Nesland J. M., Rimington C. Distribution and photosensitizing efficiency of porphyrins induced by application of exogenous 5-aminolevulinic acid in mice bearing mammary carcinoma. Int J Cancer. 1992 Sep 30;52(3):433–443. doi: 10.1002/ijc.2910520318. [DOI] [PubMed] [Google Scholar]
  22. Peng Q., Warloe T., Berg K., Moan J., Kongshaug M., Giercksky K. E., Nesland J. M. 5-Aminolevulinic acid-based photodynamic therapy. Clinical research and future challenges. Cancer. 1997 Jun 15;79(12):2282–2308. doi: 10.1002/(sici)1097-0142(19970615)79:12<2282::aid-cncr2>3.0.co;2-o. [DOI] [PubMed] [Google Scholar]
  23. Riesenberg R., Fuchs C., Kriegmair M. Photodynamic effects of 5-aminolevulinic acid-induced porphyrin on human bladder carcinoma cells in vitro. Eur J Cancer. 1996 Feb;32A(2):328–334. doi: 10.1016/0959-8049(95)00548-x. [DOI] [PubMed] [Google Scholar]
  24. Steiner R. A., Tadir Y., Tromberg B. J., Krasieva T., Ghazains A. T., Wyss P., Berns M. W. Photosensitization of the rat endometrium following 5-aminolevulinic acid induced photodynamic therapy. Lasers Surg Med. 1996;18(3):301–308. doi: 10.1002/(SICI)1096-9101(1996)18:3<301::AID-LSM12>3.0.CO;2-8. [DOI] [PubMed] [Google Scholar]
  25. Svanberg K., Wang I., Colleen S., Idvall I., Ingvar C., Rydell R., Jocham D., Diddens H., Bown S., Gregory G. Clinical multi-colour fluorescence imaging of malignant tumours--initial experience. Acta Radiol. 1998 Jan;39(1):2–9. doi: 10.1080/02841859809172141. [DOI] [PubMed] [Google Scholar]
  26. Webber J., Kessel D., Fromm D. Side effects and photosensitization of human tissues after aminolevulinic acid. J Surg Res. 1997 Feb 15;68(1):31–37. doi: 10.1006/jsre.1997.5004. [DOI] [PubMed] [Google Scholar]
  27. van den Boogert J., van Hillegersberg R., de Rooij F. W., de Bruin R. W., Edixhoven-Bosdijk A., Houtsmuller A. B., Siersema P. D., Wilson J. H., Tilanus H. W. 5-Aminolaevulinic acid-induced protoporphyrin IX accumulation in tissues: pharmacokinetics after oral or intravenous administration. J Photochem Photobiol B. 1998 Jun 15;44(1):29–38. doi: 10.1016/s1011-1344(98)00102-x. [DOI] [PubMed] [Google Scholar]

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