Skip to main content
SpringerLink
Log in

ALA- and ALA-ester-mediated Photodynamic Therapy of Human Glioma Spheroids

  • Published:
Journal of Neuro-Oncology Aims and scope Submit manuscript

Abstract

The effects of photodynamic therapy (PDT) in human glioma spheroids incubated in 5-aminolevulinic acid (ALA), or ALA esters, are investigated. Spheroid survival and growth are monitored following PDT at representative drug concentrations, light doses, and dose rates. The primary finding of this study is that the response of human glioma spheroids to PDT with lipophilic ester derivatives, such as benzyl-ALA and hexyl-ALA, is equivalent to that observed with ALA, however, this equivalency is obtained for ester concentrations 10–20 times lower than the parent compound. The enhanced efficiency of the esters is likely due to their increased membrane penetrance. Potential clinical advantages of using lipophilic esters in PDT of gliomas are discussed.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Wallner KE, Galicich JH, Krol G, Arbit E, Malkin MG: Patterns of failure following treatment for glioblastoma multiforme and anaplastic astrocytoma. Int J Radiat Oncol Biol Phys 16: 1405-1409, 1989

    Google Scholar 

  2. Johannesen TB, Watne K, Lote K, Norum J, Hennig R, Tveraa K, Hirschberg H: Intracavity fractionated balloon brachytherapy in glioblastoma. Acta Neurochir (Wien) 141: 127-133, 1999

    Google Scholar 

  3. Tsai J-C, Hsiao YY, Teng L-J, Chen C-T, Kao M-C: Comparative study on the ALA photodynamic effects of human glioma and meningioma cells. Lasers Surg Med 24: 296-305, 1999

    Google Scholar 

  4. Svaasand LO, Ellingson R: Optical properties of human brain. Photochem Photobiol 38: 293-299, 1983

    Google Scholar 

  5. Svaasand LO, Ellingson R: Optical penetration in human intracranial tumors. Photochem Photobiol 41: 73-76, 1985

    Google Scholar 

  6. Wilson BC, Muller PJ: An update on the penetration depth of 630 nm light in normal and malignant human brain tissue in vivo. Phys Med Biol 31: 1295-1297, 1986

    Google Scholar 

  7. Muller PJ, Wilson BC: Photodynamic therapy for recurrent supratentorial gliomas. Semin Surg Oncol 11: 346-354, 1995

    Google Scholar 

  8. Papovic E, Kaye A, Hill J: Photodynamic therapy of brain tumors. J Clin Laser Radiat Surg 14: 251-262, 1996

    Google Scholar 

  9. Stummer W, Stocker S, Wagner S, Stepp H, Fritsch C, Goetz C, Goetz AE, Kiefmann R, Reulen HJ: Intraoperative detection of malignant gliomas by 5-aminolevulinic acid-induced porphyrin fluorescence. Neurosurgery 42: 518-526, 1998

    Google Scholar 

  10. Stummer W, Novotny A, Stepp H, Goetz C, Bise K, Reulen HJ: Fluorescence-guided resection of glioblastoma multiforme by using 5-aminolevulinic acid-induced porphyrins: a prospective study in 52 consecutive patients. J Neurosurg 93(6): 1003-1013, 2000

    Google Scholar 

  11. Lilge L, Wilson BC: Photodynamic therapy of intracranial tissues: a preclinical comparative study of four different photosensitizers. J Clin Laser Med Surg 16: 81-92, 1998

    Google Scholar 

  12. Kloek J, Beijersbergen van Henegouwen GMJ: Prodrugs of 5-aminolevulinic acid for photodynamic therapy. Photochem Photobiol 64: 994-1000, 1996

    Google Scholar 

  13. Kloek J, Akkermans W, Beijersbergen van Henegouwen GMJ: Derivatives of 5-aminolevulinic acid for photodynamic therapy: enzymatic conversion into protoporphyrin. Photochem Photobiol 67: 150-159, 1998

    Google Scholar 

  14. Uehlinger P, Zellweger M, Wagnieres G, Juillerat-Jeanneret L, van den Bergh H, Lange N: 5-Aminolevulinic acid and its derivatives: physical chemical properties and protoporphyrin IX formation in cultured cells. J Photochem Photobiol B (Biol) 54: 72-80, 2000

    Google Scholar 

  15. Peng Q, Moan J, Warloe T, Iani V, Steen HB, Bjorseth A, Nesland JM: Build-up of esterified aminolevulinic-acid-derivatives induced porphyrin fluorescence in normal mouse skin. J Photochem Photobiol B (Biol) 34: 95-96, 1996

    Google Scholar 

  16. Biglelow CE, Mitra S, Knuechel R, Foster TH: ALA-and ALA-hexylester-induced protoporphyrin IX fluorescence and distribution in multicell tumor spheroids. Br J Cancer 85: 727-734, 2001

    Google Scholar 

  17. Lange N, Zellweger M, Forrer M, Marti A, Guillou L, Kucera P, Wagnieres G, van den Bergh H: Photodetection of early human bladder cancer based on the fluorescence of 5-aminolevulinic acid hexylester-induced protoporphyrin IX: a pilot study. Br J Cancer 80: 185-193, 1999

    Google Scholar 

  18. Foster TH, Hartley DF, Nichols MG, Hilf R: Fluence rate effects in photodynamic therapy of multicell tumor spheroids. Cancer Res 53: 1249-1254, 1993

    Google Scholar 

  19. Sutherland RM, McCredie JA, Inch WR: Growth of multicell spheroids in tissue culture as a model of nodular carcinomas. J Natl Cancer Inst 46: 113-120, 1971

    Google Scholar 

  20. Marti A, Lange N, van den Bergh H, Sedmera D, Jichlinski P, Kucera P: Optimization of the formation and distribution of protoporphyrin IX in the urothelium: an in vitro approach. J Urol 162: 546-552, 1999

    Google Scholar 

  21. Madsen SJ, Sun C-H, Tromberg BJ, Wallace VP, Hirschberg H: Photodynamic therapy of human glioma spheroids using 5-aminolevulinic acid. Photochem Photobiol 72: 128-134, 2000

    Google Scholar 

  22. Georgakoudi, I, Nichols MG, Foster TH: The mechanism of Photofrin photobleaching and its consequences for photodynamic dosimetry. Photochem Photobiol 65: 135-144, 1997

    Google Scholar 

  23. Hirschberg H, Madsen S, Lote K, Pham T, Tromberg B: An indwelling brachytherapy balloon catheter: potential use as an intracranial light applicator for photodynamic therapy. J Neuro-Oncol 44: 15-21, 1999

    Google Scholar 

  24. Madsen SJ, Sun C-H, Tromberg BJ, Hirschberg H: Development of a novel indwelling balloon applicator for optimizing light delivery in photodynamic therapy. Lasers Surg Med 29: 406-412, 2001

    Google Scholar 

  25. Madsen SJ, Svaasand LO, Tromberg BJ, Hirschberg H: Characterization of optical and thermal distributions from an intracranial balloon applicator for photodynamic therapy. Proc SPIE 4257: 41-49, 2001

    Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Neurosurgery, Rikshospitalet, Oslo, Norway

    Henry Hirschberg

  2. Beckman Laser Institute and Medical Clinic, University of California, Irvine, CA, USA

    Chung-Ho Sun & Bruce J. Tromberg

  3. Department of Health Physics, University of Nevada, Las Vegas, NV, USA

    Steen J. Madsen

  4. Las Vegas Cancer Institute, University of Nevada, Las Vegas, NV, USA

    Steen J. Madsen

Authors
  1. Henry Hirschberg
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Chung-Ho Sun
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Bruce J. Tromberg
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Steen J. Madsen
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Hirschberg, H., Sun, CH., Tromberg, B.J. et al. ALA- and ALA-ester-mediated Photodynamic Therapy of Human Glioma Spheroids. J Neurooncol 57, 1–7 (2002). https://doi.org/10.1023/A:1015784926550

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1023/A:1015784926550

Search

Navigation