SpringerLink
Log in

Repetitive 5-aminolevulinic acid-mediated photodynamic therapy on human glioma spheroids

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

Abstract

The response of human glioma spheroids to repetitive 5-aminolevulinic acid-mediated photodynamic therapy (PDT) was investigated. In all cases, light fluences were kept below toxic thresholds to simulate conditions typically found at 1–2 cm depths in brain adjacent to tumor. Significant inhibition of spheroid growth was observed following multiple PDT treatments at sub-threshold light fluences. The effect appears to be insensitive to the treatment intervals investigated (weekly or bi-monthly). In all cases, suppression of growth was observed for the duration of treatment. Low fluence rates (≤5 mW cm−2) appear to be more effective than high fluence rates (25 mW cm−2). No evidence of PDT resistance was found in this investigation.

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

Access this article

Log in via an institution

Subscribe and save

Springer+ Basic
EUR 32.99 /Month
  • Get 10 units per month
  • Download Article/Chapter or Ebook
  • 1 Unit = 1 Article or 1 Chapter
  • Cancel anytime
Subscribe now

Buy Now

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. Dougherty TJ: Photodynamic therapy. Photochem Photobiol 58: 895–900, 1993

    Google Scholar 

  2. 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 

  3. Ben-Hur E, Kol R, Riklis E, Marko R, Rosenthal I: Effect of light fluence rate on mammalian cell photosensitization by chloroaluminum phthalocyanine tetrasulphonate. Int J Radiat Biol 51: 467–476, 1987

    Google Scholar 

  4. 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 

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

    Google Scholar 

  6. Matthews W, Cook J, Mitchell JB, Perry RR, Evans S, Pass HI: In vitro photodynamic therapy of human lung cancer: investigation of dose-rate effects. Cancer Res 49: 1718–1721, 1989

    Google Scholar 

  7. van Geel IP, Oppellaar JH, Marijnissen JPA, Stewart FA: Influence of fractionation and fluence rate in photodynamic therapy with Photofrin or mTHPC. Radiat Res145: 602–609, 1996

    Google Scholar 

  8. Gibson SL, VanDerMeid KR, Murant RS, Raubertas RF, Hilf R: Effects of various photoradiation regiments on the antitumor efficacy of photodynamic therapy for R3230AC mammary carcinomas. Cancer Res 50: 7236–7241, 1990

    Google Scholar 

  9. Sitnik TM, Hampton JA, Henderson BW: Reduction of tumor oxygenation during and after photodynamic therapy in vivo: effects of fluence rate. Br J Cancer 77: 1386–1394, 1998

    Google Scholar 

  10. Sitnik TM, Henderson BW. The effect of fluence rate on tumor and normal tissue responses to photodynamic therapy. Photochem Photobiol 67: 462–466, 1998

    Google Scholar 

  11. Krishnamurthy S, Powers SK, Witmer P, Brown T: Optimal light dose for interstitial photodynamic therapy in treatment for malignant brain tumors. Lasers Surg Med 27: 224–234, 2000

    Google Scholar 

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

    Google Scholar 

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

    Google Scholar 

  14. Muller PJ, Wilson BC, Lilge LD, Yang V, Hetzel FW, Chen Q, Selker R, Abrams J: Photofrin photodynamic therapy for malignant brain tumors. Proc SPIE 4248: 34–41, 2001

    Google Scholar 

  15. Kennedy JC, Pottier RC: Endogenous protoporphyrin IX: a clinical useful photosensitizer for photodynamic therapy. J Photochem Photobiol B: Biol 14: 275–292, 1992

    Google Scholar 

  16. Kennedy JC, Pottier RH, Pross DC: Photodynamic therapy with endogenous protoporphyrin IX: basic principles and present clinical experience. J Photochem Photobiol B: Biol 6: 143–148, 1990

    Google Scholar 

  17. Malik Z, Lugaci H: Destruction of erythroleukaemic cells by photoactivation of endogenous porphyrins. Br J Cancer 56: 589–595, 1987

    Google Scholar 

  18. Peng Q, Warloe T, Berg K, Moan J, Kongshaug M, Giercksky K-E, Nesland JM: 5-Aminolevulinic acid-based photodynamic therapy: clinical research and future challenges. Cancer 79: 2282–2308

  19. Peng Q, Berg K, Moan J, Kongshaug M, Nesland JM: 5-Aminolevulinic acid-based photodynamic therapy:principles and experimental research. Photochem Photobiol 65: 235–251, 1997

    Google Scholar 

  20. 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 

  21. Hebeda KM, Saarnak AE, Olivo M, Sterenborg HJ, Wolbers JG: 5-Aminolevulinic acid induced endogenous porphyrin fluorescence in 9L and C6 brain tumours and in the normal rat brain. Acta Neurochir 140: 503–513, 1998

    Google Scholar 

  22. Lilge L, Portnoy M, Wilson BC: Apoptosis induced in vivo by photodynamic therapy in normal brain and intracranial tumor tissue. Br J Cancer 83: 1110–1117, 2000

    Google Scholar 

  23. Obwegeser A, Jakober R, Kostron H: Uptake and kinetics of 14C-labelled meta-tetrahydroxylchlorin and 5-aminolaevulinic acid in the C6 rat glioma model. Br J Cancer 78: 733–738, 1998

    Google Scholar 

  24. Stummer W, Stocker S, Novotny A, Heimann A, Sauer O, Kempski O, Plesnila N, Wietzorrek J, Reulen HJ: In vitro and in vivo porphyrin accumulation by C6 glioma cells after exposure to 5-aminolevulinic acid. J Photochem Photobiol B: Biol 45: 160–169, 1998

    Google Scholar 

  25. 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 acidinduced porphyrin fluorescence. Neurosurg 42: 518–526, 1998

    Google Scholar 

  26. Terr L, Weiner LP: An autoradiographic study of 5-aminolevulinic acid uptake by mouse brain. Exp Neurol 79: 564–568, 1983

    Google Scholar 

  27. 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: 1003–1013, 2000

    Google Scholar 

  28. 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 

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

    Google Scholar 

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

    Google Scholar 

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

    Google Scholar 

  32. 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 

  33. Webber J, Kessel D, Fromm D: Side effects and photosensitization of human tissues after aminolevulinic acid. J Surg Res 68: 31–37, 1997

    Google Scholar 

  34. Georgakoudi I, Nichols MG, Foster TH: The mechanism of Photofrin photobleaching and its consequences for photodynamic dosimetry. Photochem Photobiol 65: 135–144, 1999

    Google Scholar 

  35. Bigelow 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 

  36. 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 

Download references

Author information

Authors and Affiliations

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

    Steen J. Madsen

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

    Steen J. Madsen

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

    Chung-Ho Sun & Bruce J. Tromberg

  4. Department of Neurosurgery, Rikshospitalet, Oslo, Norway

    Henry Hirschberg

Authors
  1. Steen J. Madsen
    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. Henry Hirschberg
    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

Madsen, S.J., Sun, CH., Tromberg, B.J. et al. Repetitive 5-aminolevulinic acid-mediated photodynamic therapy on human glioma spheroids. J Neurooncol 62, 243–250 (2003). https://doi.org/10.1023/A:1023362011705

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1023/A:1023362011705

Search

Navigation