Advertisement

Journal of Neuro-Oncology

, Volume 141, Issue 3, pp 595–607 | Cite as

5-aminolevulinic acid photodynamic therapy for the treatment of high-grade gliomas

  • K. Mahmoudi
  • K. L. Garvey
  • A. Bouras
  • G. Cramer
  • H. Stepp
  • J. G. Jesu Raj
  • D. Bozec
  • T. M. BuschEmail author
  • C. G. HadjipanayisEmail author
Topic Review

Abstract

Introduction

Photodynamic therapy (PDT) is a two-step treatment involving the administration of a photosensitive agent followed by its activation at a specific light wavelength for targeting of tumor cells.

Materials/Methods

A comprehensive review of the literature was performed to analyze the indications for PDT, mechanisms of action, use of different photosensitizers, the immunomodulatory effects of PDT, and both preclinical and clinical studies for use in high-grade gliomas (HGGs).

Results

PDT has been approved by the United States Food and Drug Administration (FDA) for the treatment of premalignant and malignant diseases, such as actinic keratoses, Barrett’s esophagus, esophageal cancers, and endobronchial non-small cell lung cancers, as well as for the treatment of choroidal neovascularization. In neuro-oncology, clinical trials are currently underway to demonstrate PDT efficacy against a number of malignancies that include HGGs and other brain tumors. Both photosensitizers and photosensitizing precursors have been used for PDT. 5-aminolevulinic acid (5-ALA), an intermediate in the heme synthesis pathway, is a photosensitizing precursor with FDA approval for PDT of actinic keratosis and as an intraoperative imaging agent for fluorescence-guided visualization of malignant tissue during glioma surgery. New trials are underway to utilize 5-ALA as a therapeutic agent for PDT of the intraoperative resection cavity and interstitial PDT for inoperable HGGs.

Conclusion

PDT remains a promising therapeutic approach that requires further study in HGGs. Use of 5-ALA PDT permits selective tumor targeting due to the intracellular metabolism of 5-ALA. The immunomodulatory effects of PDT further strengthen its use for treatment of HGGs and requires a better understanding. The combination of PDT with adjuvant therapies for HGGs will need to be studied in randomized, controlled studies.

Keywords

5-Aminolevulinic acid (5-ALA) Photodynamic therapy GBM Protoporphyrin IX (PpIX) High grade glioma Photosensitizer 

Notes

Acknowledgements

Authors TMB and GMC acknowledge NIH/NCI grants P01-CA087971 and R01-CA85831 for support during the preparation of this manuscript.

References

  1. 1.
    Ostrom QT, Gittleman H, Xu J, Kromer C, Wolinsky Y, Kruchko C, Barnholtz-Sloan JS (2016) CBTRUS statistical report: primary brain and other central nervous system tumors diagnosed in the United States in 2009–2013. Neuro-Oncology 18:v1–v75.  https://doi.org/10.1093/neuonc/now207 Google Scholar
  2. 2.
    Ostrom QT, Gittleman H, Liao P, Vecchione-Koval T, Wolinsky Y, Kruchko C, Barnholtz-Sloan JS (2017) CBTRUS statistical report: primary brain and other central nervous system tumors diagnosed in the United States in 2010–2014. Neuro-Oncology 19:v1–v88.  https://doi.org/10.1093/neuonc/nox158 Google Scholar
  3. 3.
    Louis DN, Perry A, Reifenberger G, von Deimling A, Figarella-Branger D, Cavenee WK, Ohgaki H, Wiestler OD, Kleihues P, Ellison DW (2016) The 2016 World Health Organization classification of tumors of the central nervous system: a summary. Acta Neuropathol 131:803–820.  https://doi.org/10.1007/s00401-016-1545-1 Google Scholar
  4. 4.
    Stupp R, Hegi ME, Mason WP, van den Bent MJ, Taphoorn MJB, Janzer RC, Ludwin SK, Allgeier A, Fisher B, Belanger K, Hau P, Brandes AA, Gijtenbeek J, Marosi C, Vecht CJ, Mokhtari K, Wesseling P, Villa S, Eisenhauer E, Gorlia T, Weller M, Lacombe D, Cairncross JG, Mirimanoff R-O (2009) Effects of radiotherapy with concomitant and adjuvant temozolomide versus radiotherapy alone on survival in glioblastoma in a randomised phase III study: 5-year analysis of the EORTC-NCIC trial. Lancet Oncol 10:459–466.  https://doi.org/10.1016/S1470-2045(09)70025-7 Google Scholar
  5. 5.
    Stupp R, Mason WP, van den Bent MJ, Weller M, Fisher B, Taphoorn MJB, Belanger K, Brandes AA, Marosi C, Bogdahn U, Curschmann J, Janzer RC, Ludwin SK, Gorlia T, Allgeier A, Lacombe D, Cairncross JG, Eisenhauer E, Mirimanoff RO (2005) Radiotherapy plus concomitant and adjuvant temozolomide for glioblastoma. N Engl J Med 352:987–996.  https://doi.org/10.1056/NEJMoa043330 Google Scholar
  6. 6.
    Dong X, Noorbakhsh A, Hirshman BR, Zhou T, Tang JA, Chang DC, Carter BS, Chen CC (2016) Survival trends of grade I, II, and III astrocytoma patients and associated clinical practice patterns between 1999 and 2010: a SEER-based analysis. Neuro-Oncology Pract 3:29–38.  https://doi.org/10.1093/nop/npv016 Google Scholar
  7. 7.
    Smoll NR, Hamilton B (2014) Incidence and relative survival of anaplastic astrocytomas. Neuro-Oncology 16:1400–1407.  https://doi.org/10.1093/neuonc/nou053 Google Scholar
  8. 8.
  9. 9.
    Lee Titsworth W, Murad GJ, Hoh BL, Rahman M (2014) Fighting fire with fire: the revival of thermotherapy for gliomas. Anticancer Res 34:565–574Google Scholar
  10. 10.
    Sun J, Guo M, Pang H, Qi J, Zhang J, Ge Y (2013) Treatment of malignant glioma using hyperthermia. Neural Regen Res 8:2775–2782.  https://doi.org/10.3969/j.issn.1673-5374.2013.29.009 Google Scholar
  11. 11.
    Reznik E, Smith AW, Taube S, Mann J, Yondorf MZ, Parashar B, Wernicke AG (2018) Radiation and immunotherapy in high-grade gliomas: where do we stand? Am J Clin Oncol 41:197–212.  https://doi.org/10.1097/coc.0000000000000406 Google Scholar
  12. 12.
    Akimoto J (2016) Photodynamic therapy for malignant brain tumors. Neurol Med-Chir 56:151–157.  https://doi.org/10.2176/nmc.ra.2015-0296 Google Scholar
  13. 13.
    Stepp H, Stummer W (2018) 5-ALA in the management of malignant glioma. Lasers Surg Med 50:399–419.  https://doi.org/10.1002/lsm.22933 Google Scholar
  14. 14.
    DM D, HJ S (1991) A history of photodynamic therapy. Australian and New Zealand. J Surg 61:340–348.  https://doi.org/10.1111/j.1445-2197.1991.tb00230.x Google Scholar
  15. 15.
    Castano AP, Demidova TN, Hamblin MR (2004) Mechanisms in photodynamic therapy: part one-photosensitizers, photochemistry and cellular localization. Photodiagn Photodyn Ther 1:279–293.  https://doi.org/10.1016/S1572-1000(05)00007-4 Google Scholar
  16. 16.
    Castano AP, Demidova TN, Hamblin MR (2005) Mechanisms in photodynamic therapy: part two—cellular signaling, cell metabolism and modes of cell death. Photodiagn Photodyn Ther 2:1–23.  https://doi.org/10.1016/S1572-1000(05)00030-X Google Scholar
  17. 17.
    Kawase Y, Iseki H (2013) Parameter-finding studies of photodynamic therapy for approval in Japan and the USA. Photodiagn Photodyn Ther 10:434–445.  https://doi.org/10.1016/j.pdpdt.2013.03.001 Google Scholar
  18. 18.
  19. 19.
    Kessel D (2018) Apoptosis, paraptosis and autophagy: death and survival pathways associated with photodynamic therapy. Photochem Photobiol.  https://doi.org/10.1111/php.12952 Google Scholar
  20. 20.
    Mroz P, Yaroslavsky A, Kharkwal GB, Hamblin MR (2011) Cell death pathways in photodynamic therapy of cancer. Cancers (Basel) 3:2516–2539.  https://doi.org/10.3390/cancers3022516 Google Scholar
  21. 21.
    Hirschberg H, Sun C-H, Tromberg BJ, Yeh AT, Madsen SJ (2004) Enhanced cytotoxic effects of 5-aminolevulinic acid-mediated photodynamic therapy by concurrent hyperthermia in glioma spheroids. J Neuro-Oncol 70:289–299.  https://doi.org/10.1007/s11060-004-9161-7 Google Scholar
  22. 22.
    Karmakar S, Banik NL, Patel SJ, Ray SK (2007) 5-Aminolevulinic acid-based photodynamic therapy suppressed survival factors and activated proteases for apoptosis in human glioblastoma U87MG cells. Neurosci Lett 415:242–247.  https://doi.org/10.1016/j.neulet.2007.01.071 Google Scholar
  23. 23.
    Coupienne I, Fettweis G, Rubio N, Agostinis P, Piette J (2011) 5-ALA-PDT induces RIP3-dependent necrosis in glioblastoma. Photochemical & photobiological sciences: official journal of the European Photochemistry Association and the European Society for Photobiology. Photochem Photobiol Sci 10: 1868–1878  https://doi.org/10.1039/c1pp05213f Google Scholar
  24. 24.
    Coupienne I, Bontems S, Dewaele M, Rubio N, Habraken Y, Fulda S, Agostinis P, Piette J (2011) NF-kappaB inhibition improves the sensitivity of human glioblastoma cells to 5-aminolevulinic acid-based photodynamic therapy. Biochem Pharmacol 81:606–616.  https://doi.org/10.1016/j.bcp.2010.12.015 Google Scholar
  25. 25.
    Cengel KA, Simone CB, Busch TM Vascular effects of photodynamic therapy for tumors. Handbook of photodynamic therapy. University of Toronto, Canada, pp 335–364Google Scholar
  26. 26.
    Castano AP, Mroz P, Hamblin MR (2006) Photodynamic therapy and anti-tumour immunity. Nat Rev Cancer 6:535–545.  https://doi.org/10.1038/nrc1894 Google Scholar
  27. 27.
    Garg AD, Nowis D, Golab J, Agostinis P (2010) Photodynamic therapy: illuminating the road from cell death towards anti-tumour immunity. Apoptosis 15:1050–1071.  https://doi.org/10.1007/s10495-010-0479-7 Google Scholar
  28. 28.
    Yi W, Xu HT, Tian DF, Wu LQ, Zhang SQ, Wang L, Ji BW, Zhu XN, Okechi H, Liu G, Chen QX (2015) Photodynamic therapy mediated by 5-aminolevulinic acid suppresses gliomas growth by decreasing the microvessels. J Huazhong Univ Sci Technol Med Sci 35:259–264.  https://doi.org/10.1007/s11596-015-1421-6 Google Scholar
  29. 29.
    Anzengruber F, Avci P, de Freitas LF, Hamblin MR (2015) T-cell mediated anti-tumor immunity after photodynamic therapy: why does it not always work and how can we improve it? Photochem Photobiol Sci 14: 1492–1509  https://doi.org/10.1039/c4pp00455h Google Scholar
  30. 30.
    Hirschberg H, Berg K, Peng Q (2018) Photodynamic therapy mediated immune therapy of brain tumors. Neuroimmunol Neuroinflammation 5:27.  https://doi.org/10.20517/2347-8659.2018.31 Google Scholar
  31. 31.
    Etminan N, Peters C, Lakbir D, Bunemann E, Borger V, Sabel MC, Hanggi D, Steiger HJ, Stummer W, Sorg RV (2011) Heat-shock protein 70-dependent dendritic cell activation by 5-aminolevulinic acid-mediated photodynamic treatment of human glioblastoma spheroids in vitro. Br J Cancer 105:961–969.  https://doi.org/10.1038/bjc.2011.327 Google Scholar
  32. 32.
    Li F, Cheng Y, Lu J, Hu R, Wan Q, Feng H (2011) Photodynamic therapy boosts anti-glioma immunity in mice: a dependence on the activities of T cells and complement C3. J Cell Biochem 112:3035–3043.  https://doi.org/10.1002/jcb.23228 Google Scholar
  33. 33.
    Plaetzer K, Krammer B, Berlanda J, Berr F, Kiesslich T (2009) Photophysics and photochemistry of photodynamic therapy: fundamental aspects. Lasers Med Sci 24:259–268.  https://doi.org/10.1007/s10103-008-0539-1 Google Scholar
  34. 34.
    Stables GI, Ash DV (1995) Photodynamic therapy. Cancer Treat Rev 21:311–323Google Scholar
  35. 35.
    Wang HW, Zhu TC, Putt ME, Solonenko M, Metz J, Dimofte A, Miles J, Fraker DL, Glatstein E, Hahn SM, Yodh AG (2005) Broadband reflectance measurements of light penetration, blood oxygenation, hemoglobin concentration, and drug concentration in human intraperitoneal tissues before and after photodynamic therapy. J Biomed Opt 10:14004.  https://doi.org/10.1117/1.1854679 Google Scholar
  36. 36.
    Quirk BJ, Brandal G, Donlon S, Vera JC, Mang TS, Foy AB, Lew SM, Girotti AW, Jogal S, LaViolette PS, Connelly JM, Whelan HT (2015) Photodynamic therapy (PDT) for malignant brain tumors – Where do we stand? Photodiagn Photodyn Ther 12: 530–544  https://doi.org/10.1016/j.pdpdt.2015.04.009 Google Scholar
  37. 37.
    Mallidi S, Anbil S, Bulin AL, Obaid G, Ichikawa M, Hasan T (2016) Beyond the barriers of light penetration: strategies, perspectives and possibilities for photodynamic therapy. Theranostics 6:2458–2487.  https://doi.org/10.7150/thno.16183 Google Scholar
  38. 38.
    Quon H, Grossman CE, Finlay JC, Zhu TC, Clemmens CS, Malloy KM, Busch TM (2011) Photodynamic therapy in the management of pre-malignant head and neck mucosal dysplasia and microinvasive carcinoma. Photodiagn Photodyn Ther 8:75–85.  https://doi.org/10.1016/j.pdpdt.2011.01.001 Google Scholar
  39. 39.
    Leroy HA, Vermandel M, Vignion-Dewalle AS, Leroux B, Maurage CA, Duhamel A, Mordon S, Reyns N (2017) Interstitial photodynamic therapy and glioblastoma: light fractionation in a preclinical model. Lasers Surg Med 49:506–515.  https://doi.org/10.1002/lsm.22620 Google Scholar
  40. 40.
    Hirschberg H, Spetalen S, Carper S, Hole P, Tillung T, Madsen S (2006) Minimally invasive photodynamic therapy (PDT) for ablation of experimental rat glioma. Minim Invasive Neurosurg 49:135–142.  https://doi.org/10.1055/s-2006-932216 Google Scholar
  41. 41.
    Dupont C, Mordon S, Deleporte P, Reyns N, Vermandel M (2017) A novel device for intraoperative photodynamic therapy dedicated to glioblastoma treatment. Future Oncol 13:2441–2454.  https://doi.org/10.2217/fon-2017-0261 Google Scholar
  42. 42.
    Reyns N (2017) INtraoperative photoDYnamic Therapy of GliOblastoma (INDYGO). https://clinicaltrials.gov/ct2/show/record/NCT03048240?view=record
  43. 43.
    Bechet D, Mordon SR, Guillemin F, Barberi-Heyob MA (2014) Photodynamic therapy of malignant brain tumours: a complementary approach to conventional therapies. Cancer Treat Rev 40:229–241.  https://doi.org/10.1016/j.ctrv.2012.07.004 Google Scholar
  44. 44.
    Davies N, Wilson BC (2007) Interstitial in vivo ALA-PpIX mediated metronomic photodynamic therapy (mPDT) using the CNS-1 astrocytoma with bioluminescence monitoring. Photodiagn Photodyn Ther 4:202–212.  https://doi.org/10.1016/j.pdpdt.2007.06.002 Google Scholar
  45. 45.
    Beck TJ, Kreth FW, Beyer W, Mehrkens JH, Obermeier A, Stepp H, Stummer W, Baumgartner R (2007) Interstitial photodynamic therapy of nonresectable malignant glioma recurrences using 5-aminolevulinic acid induced protoporphyrin IX. Lasers Surg Med 39:386–393.  https://doi.org/10.1002/lsm.20507 Google Scholar
  46. 46.
    Yassine A-A, Kingsford W, Xu Y, Cassidy J, Lilge L, Betz V (2018) Automatic interstitial photodynamic therapy planning via convex optimization. Biomed Opt Express 9:898–920.  https://doi.org/10.1364/BOE.9.000898 Google Scholar
  47. 47.
    Shafirstein G, Bellnier D, Oakley E, Hamilton S, Potasek M, Beeson K, Parilov E (2017) Interstitial Photodynamic Therapy-A Focused Review. Cancers (Basel) 9  https://doi.org/10.3390/cancers9020012
  48. 48.
    Stummer W, Pichlmeier U, Meinel T, Wiestler OD, Zanella F, Reulen H-J (2006) Fluorescence-guided surgery with 5-aminolevulinic acid for resection of malignant glioma: a randomised controlled multicentre phase III trial. Lancet Oncol 7:392–401.  https://doi.org/10.1016/S1470-2045(06)70665-9 Google Scholar
  49. 49.
    Lee I, Kalkanis S, Hadjipanayis CG (2016) Stereotactic Laser Interstitial Thermal Therapy for Recurrent High-Grade Gliomas. Neurosurgery 79(Suppl 1):S24–Ss34.  https://doi.org/10.1227/neu.0000000000001443 Google Scholar
  50. 50.
    Senders JT, Muskens IS, Schnoor R, Karhade AV, Cote DJ, Smith TR, Broekman ML (2017) Agents for fluorescence-guided glioma surgery: a systematic review of preclinical and clinical results. Acta Neurochir 159:151–167.  https://doi.org/10.1007/s00701-016-3028-5 Google Scholar
  51. 51.
    Lakomkin N, Hadjipanayis CG (2018) Fluorescence-guided surgery for high-grade gliomas. J Surg Oncol 118:356–361  https://doi.org/10.1002/jso.25154 Google Scholar
  52. 52.
    He J, Yang L, Yi W, Fan W, Wen Y, Miao X, Xiong L (2017) Combination of fluorescence-guided surgery with photodynamic therapy for the treatment of cancer. Mol Imaging 16:1536012117722911.  https://doi.org/10.1177/1536012117722911 Google Scholar
  53. 53.
    Kou J, Dou D, Yang L (2017) Porphyrin photosensitizers in photodynamic therapy and its applications. Oncotarget 8:81591–81603.  https://doi.org/10.18632/oncotarget.20189 Google Scholar
  54. 54.
    Bellnier DA, Greco WR, Loewen GM, Nava H, Oseroff AR, Dougherty TJ (2006) Clinical pharmacokinetics of the PDT photosensitizers porfimer sodium (Photofrin), 2-[1-hexyloxyethyl]-2-devinyl pyropheophorbide-a (Photochlor) and 5-ALA-induced protoporphyrin IX. Lasers Surg Med 38:439–444.  https://doi.org/10.1002/lsm.20340 Google Scholar
  55. 55.
    Ormond AB, Freeman HS (2013) Dye sensitizers for photodynamic therapy. Materials (Basel) 6:817–840.  https://doi.org/10.3390/ma6030817 Google Scholar
  56. 56.
    Zhang J, Jiang C, Figueiro Longo JP, Azevedo RB, Zhang H, Muehlmann LA (2018) An updated overview on the development of new photosensitizers for anticancer photodynamic therapy. Acta Pharm Sin B 8:137–146.  https://doi.org/10.1016/j.apsb.2017.09.003 Google Scholar
  57. 57.
    Hiramatsu R, Kawabata S, Miyatake S, Kuroiwa T, Easson MW, Vicente MG (2011) Application of a novel boronated porphyrin (H(2)OCP) as a dual sensitizer for both PDT and BNCT. Lasers Surg Med 43:52–58.  https://doi.org/10.1002/lsm.21026 Google Scholar
  58. 58.
    Hill JS, Kahl SB, Stylli SS, Nakamura Y, Koo MS, Kaye AH (1995) Selective tumor kill of cerebral glioma by photodynamic therapy using a boronated porphyrin photosensitizer. Proc Natl Acad Sci USA 92:12126–12130Google Scholar
  59. 59.
    Hill JS, Kahl SB, Kaye AH, Stylli SS, Koo MS, Gonzales MF, Vardaxis NJ, Johnson CI (1992) Selective tumor uptake of a boronated porphyrin in an animal model of cerebral glioma. Proc Natl Acad Sci USA 89:1785–1789Google Scholar
  60. 60.
    Josefsen LB, Boyle RW (2008) Photodynamic therapy: novel third-generation photosensitizers one step closer? Br J Pharmacol 154:1–3.  https://doi.org/10.1038/bjp.2008.98 Google Scholar
  61. 61.
    Zhang J, Jiang C, Figueiró Longo JP, Azevedo RB, Zhang H, Muehlmann LA (2018) An updated overview on the development of new photosensitizers for anticancer photodynamic therapy. Acta Pharm Sin B 8:137–146.  https://doi.org/10.1016/j.apsb.2017.09.003 Google Scholar
  62. 62.
    Bechet D, Auger F, Couleaud P, Marty E, Ravasi L, Durieux N, Bonnet C, Plenat F, Frochot C, Mordon S, Tillement O, Vanderesse R, Lux F, Perriat P, Guillemin F, Barberi-Heyob M (2015) Multifunctional ultrasmall nanoplatforms for vascular-targeted interstitial photodynamic therapy of brain tumors guided by real-time MRI. Nanomedicine 11: 657–670  https://doi.org/10.1016/j.nano.2014.12.007 Google Scholar
  63. 63.
    Thomas E, Colombeau L, Gries M, Peterlini T, Mathieu C, Thomas N, Boura C, Frochot C, Vanderesse R, Lux F, Barberi-Heyob M, Tillement O (2017) Ultrasmall AGuIX theranostic nanoparticles for vascular-targeted interstitial photodynamic therapy of glioblastoma. Int J Nanomed 12:7075–7088.  https://doi.org/10.2147/ijn.s141559 Google Scholar
  64. 64.
    Reddy GR, Bhojani MS, McConville P, Moody J, Moffat BA, Hall DE, Kim G, Koo YE, Woolliscroft MJ, Sugai JV, Johnson TD, Philbert MA, Kopelman R, Rehemtulla A, Ross BD (2006) Vascular targeted nanoparticles for imaging and treatment of brain tumors. Clin Cancer Res 12:6677–6686.  https://doi.org/10.1158/1078-0432.Ccr-06-0946 Google Scholar
  65. 65.
    Meyers JD, Cheng Y, Broome AM, Agnes RS, Schluchter MD, Margevicius S, Wang X, Kenney ME, Burda C, Basilion JP (2015) Peptide-Targeted Gold Nanoparticles for Photodynamic Therapy of Brain Cancer. Part Part Syst Charact 32: 448–457  https://doi.org/10.1002/ppsc.201400119 Google Scholar
  66. 66.
    Rajora MA, Ding L, Valic M, Jiang W, Overchuk M, Chen J, Zheng G (2017) Tailored theranostic apolipoprotein E3 porphyrin-lipid nanoparticles target glioblastoma †Electronic supplementary information (ESI) available. See DOI: 10.1039/c7sc00732a Click here for additional data file. Chem Sci 8:5371–5384.  https://doi.org/10.1039/c7sc00732a Google Scholar
  67. 67.
    Tang XL, Wu J, Lin BL, Cui S, Liu HM, Yu RT, Shen XD, Wang TW, Xia W (2018) Near-infrared light-activated red-emitting upconverting nanoplatform for T1-weighted magnetic resonance imaging and photodynamic therapy. Acta Biomater 74:360–373.  https://doi.org/10.1016/j.actbio.2018.05.017 Google Scholar
  68. 68.
    Tsai YC, Vijayaraghavan P, Chiang WH, Chen HH, Liu TI, Shen MY, Omoto A, Kamimura M, Soga K, Chiu HC (2018) Targeted delivery of functionalized upconversion nanoparticles for externally triggered photothermal/photodynamic therapies of brain glioblastoma. Theranostics 8:1435–1448.  https://doi.org/10.7150/thno.22482 Google Scholar
  69. 69.
    Hadjipanayis CG, Widhalm G, Stummer W (2015) What is the surgical benefit of utilizing 5-ALA for fluorescence-guided surgery of malignant gliomas? Neurosurgery 77:663–673.  https://doi.org/10.1227/NEU.0000000000000929 Google Scholar
  70. 70.
    Valdes PA, Bekelis K, Harris BT, Wilson BC, Leblond F, Kim A, Simmons NE, Erkmen K, Paulsen KD, Roberts DW (2014) 5-Aminolevulinic acid-induced protoporphyrin IX fluorescence in meningioma: qualitative and quantitative measurements in vivo. Neurosurgery 10:74–83.  https://doi.org/10.1227/NEU.0000000000000117 Google Scholar
  71. 71.
    Stummer W, Reulen HJ, Novotny A, Stepp H, Tonn JC (2003) Fluorescence-guided resections of malignant gliomas–an overview. Acta neurochirurgica Supplement 88:9–12Google Scholar
  72. 72.
    Teng L, Nakada M, Zhao SG, Endo Y, Furuyama N, Nambu E, Pyko IV, Hayashi Y, Hamada JI (2011) Silencing of ferrochelatase enhances 5-aminolevulinic acid-based fluorescence and photodynamic therapy efficacy. Br J Cancer 104:798–807.  https://doi.org/10.1038/bjc.2011.12 Google Scholar
  73. 73.
    Yang X, Li W, Palasuberniam P, Myers KA, Wang C, Chen B (2015) Effects of silencing heme biosynthesis enzymes on 5-Aminolevulinic acid-mediated protoporphyrin IX fluorescence and photodynamic therapy. Photochem Photobiol 91:923–930.  https://doi.org/10.1111/php.12454 Google Scholar
  74. 74.
    Kaneko S, Kaneko S (2016) Fluorescence-guided resection of malignant glioma with 5-ALA. Int J Biomed Imaging 2016: 11  https://doi.org/10.1155/2016/6135293
  75. 75.
    Johansson A, Faber F, Kniebuhler G, Stepp H, Sroka R, Egensperger R, Beyer W, Kreth FW (2013) Protoporphyrin IX fluorescence and photobleaching during interstitial photodynamic therapy of malignant gliomas for early treatment prognosis. Lasers Surg Med 45:225–234.  https://doi.org/10.1002/lsm.22126 Google Scholar
  76. 76.
    Ahn PH, Finlay JC, Gallagher-Colombo SM, Quon H, O’Malley BW Jr, Weinstein GS, Chalian A, Malloy K, Sollecito T, Greenberg M, Simone CB 2nd, McNulty S, Lin A, Zhu TC, Livolsi V, Feldman M, Mick R, Cengel KA, Busch TM (2018) Lesion oxygenation associates with clinical outcomes in premalignant and early stage head and neck tumors treated on a phase 1 trial of photodynamic therapy. Photodiagn Photodyn Ther 21:28–35.  https://doi.org/10.1016/j.pdpdt.2017.10.015 Google Scholar
  77. 77.
    Tetard M-C, Vermandel M, Mordon S, Lejeune J-P, Reyns N (2014) Experimental use of photodynamic therapy in high grade gliomas: a review focused on 5-aminolevulinic acid. Photodiagn Photodyn Ther 11:319–330.  https://doi.org/10.1016/j.pdpdt.2014.04.004 Google Scholar
  78. 78.
    Stummer W, Stocker S, Novotny A, Heimann A, Sauer O, Kempski O, Plesnila N, Wietzorrek J, Reulen HJ (1998) In vitro and in vivo porphyrin accumulation by C6 glioma cells after exposure to 5-aminolevulinic acid. J Photochem Photobiol B 45:160–169Google Scholar
  79. 79.
    Tsai JC, Hsiao YY, Teng LJ, Chen CT, Kao MC (1999) Comparative study on the ALA photodynamic effects of human glioma and meningioma cells. Lasers Surg Med 24:296–305Google Scholar
  80. 80.
    Madsen Steen J, Sun C-H, Tromberg Bruce J, Hirschberg H (2001) Development of a novel indwelling balloon applicator for optimizing light delivery in photodynamic therapy. Lasers Surg Med 29:406–412.  https://doi.org/10.1002/lsm.10005 Google Scholar
  81. 81.
    Busch TM, Xing X, Yu G, Yodh A, Wileyto EP, Wang HW, Durduran T, Zhu TC, Wang KK (2009) Fluence rate-dependent intratumor heterogeneity in physiologic and cytotoxic responses to Photofrin photodynamic therapy. Photochem Photobiol Sci 8:1683–1693.  https://doi.org/10.1039/b9pp00004f Google Scholar
  82. 82.
    Hirschberg H, Sun C-H, Tromberg BJ, Madsen SJ (2002) ALA- and ALA-ester-mediated photodynamic therapy of human glioma spheroids. J Neuro-Oncol 57:1–7.  https://doi.org/10.1023/A:1015784926550 Google Scholar
  83. 83.
    Olzowy B, Hundt CS, Stocker S, Bise K, Reulen HJ, Stummer W (2002) Photoirradiation therapy of experimental malignant glioma with 5-aminolevulinic acid. J Neurosurg 97:970–976.  https://doi.org/10.3171/jns.2002.97.4.0970 Google Scholar
  84. 84.
    Hirschberg H, Sorensen DR, Angell-Petersen E, Peng Q, Tromberg B, Sun CH, Spetalen S, Madsen S (2006) Repetitive photodynamic therapy of malignant brain tumors. J Environ Pathol Toxicol Oncol 25:261–279Google Scholar
  85. 85.
    Tetard M-C, Vermandel M, Leroy H-A, Leroux B, Maurage C-A, Lejeune J-P, Mordon S, Reyns N (2016) Interstitial 5-ALA photodynamic therapy and glioblastoma: Preclinical model development and preliminary results. Photodiagn Photodyn Ther 13:218–224.  https://doi.org/10.1016/j.pdpdt.2015.07.169 Google Scholar
  86. 86.
    Hefti M, Albert I, Luginbuehl V (2012) Phenytoin reduces 5-aminolevulinic acid-induced protoporphyrin IX accumulation in malignant glioma cells. J Neuro-Oncol 108:443–450.  https://doi.org/10.1007/s11060-012-0857-9 Google Scholar
  87. 87.
    Lawrence JE, Steele CJ, Rovin RA, Belton RJ, Winn RJ (2016) Dexamethasone alone and in combination with desipramine, phenytoin, valproic acid or levetiracetam interferes with 5-ALA-mediated PpIX production and cellular retention in glioblastoma cells. J Neuro-Oncol 127:15–21.  https://doi.org/10.1007/s11060-015-2012-x Google Scholar
  88. 88.
    Grabb PA, Gilbert MR (1995) Neoplastic and pharmacological influence on the permeability of an in vitro blood-brain barrier. J Neurosurg 82:1053–1058.  https://doi.org/10.3171/jns.1995.82.6.1053 Google Scholar
  89. 89.
    Wang W, Tabu K, Hagiya Y, Sugiyama Y, Kokubu Y, Murota Y, Ogura S-i, Taga T (2017) Enhancement of 5-aminolevulinic acid-based fluorescence detection of side population-defined glioma stem cells by iron chelation. Sci Rep 7: 42070  https://doi.org/10.1038/srep42070.https://www.nature.com/articles/srep42070#supplementary-information
  90. 90.
    Blake E, Curnow A (2010) The hydroxypyridinone iron chelator CP94 can enhance PpIX-induced PDT of cultured human glioma cells. Photochem Photobiol 86:1154–1160.  https://doi.org/10.1111/j.1751-1097.2010.00770.x Google Scholar
  91. 91.
    Chen X, Wang C, Teng L, Liu Y, Chen X, Yang G, Wang L, Liu H, Liu Z, Zhang D, Zhang Y, Guan H, Li X, Fu C, Zhao B, Yin F, Zhao S (2014) Calcitriol enhances 5-aminolevulinic acid-induced fluorescence and the effect of photodynamic therapy in human glioma. Acta Oncol 53:405–413.  https://doi.org/10.3109/0284186x.2013.819993 Google Scholar
  92. 92.
    Ishikawa T, Kajimoto Y, Inoue Y, Ikegami Y, Kuroiwa T (2015) Critical role of ABCG2 in ALA-photodynamic diagnosis and therapy of human brain tumor. Adv Cancer Res 125:197–216.  https://doi.org/10.1016/bs.acr.2014.11.008 Google Scholar
  93. 93.
    Fisher CJ, Niu C, Foltz W, Chen Y, Sidorova-Darmos E, Eubanks JH, Lilge L (2017) ALA-PpIX mediated photodynamic therapy of malignant gliomas augmented by hypothermia. PLoS ONE 12:e0181654.  https://doi.org/10.1371/journal.pone.0181654 Google Scholar
  94. 94.
    Semyachkina-Glushkovskaya O, Kurths J, Borisova E, Sokolovski S, Mantareva V, Angelov I, Shirokov A, Navolokin N, Shushunova N, Khorovodov A, Ulanova M, Sagatova M, Agranivich I, Sindeeva O, Gekalyuk A, Bodrova A, Rafailov E (2017) Photodynamic opening of blood-brain barrier. Biomed Opt Express 8:5040–5048.  https://doi.org/10.1364/BOE.8.005040 Google Scholar
  95. 95.
    Kostron H, Fritsch E, Grunert V (1988) Photodynamic therapy of malignant brain tumours: a phase I/II trial. Br J Neurosurg 2:241–248Google Scholar
  96. 96.
    Rosenthal MA, Kavar B, Hill JS, Morgan DJ, Nation RL, Stylli SS, Basser RL, Uren S, Geldard H, Green MD, Kahl SB, Kaye AH (2001) Phase I and pharmacokinetic study of photodynamic therapy for high-grade gliomas using a novel boronated porphyrin. J Clin Oncol 19:519–524.  https://doi.org/10.1200/jco.2001.19.2.519 Google Scholar
  97. 97.
    Schmidt MH, Meyer GA, Reichert KW, Cheng J, Krouwer HG, Ozker K, Whelan HT (2004) Evaluation of photodynamic therapy near functional brain tissue in patients with recurrent brain tumors. J Neurooncol 67:201–207Google Scholar
  98. 98.
    Lyons M, Phang I, Eljamel S (2012) The effects of PDT in primary malignant brain tumours could be improved by intraoperative radiotherapy. Photodiagn Photodyn Ther 9:40–45.  https://doi.org/10.1016/j.pdpdt.2011.12.001 Google Scholar
  99. 99.
    Eljamel MS, Goodman C, Moseley H (2008) ALA and Photofrin fluorescence-guided resection and repetitive PDT in glioblastoma multiforme: a single centre Phase III randomised controlled trial. Lasers Med Sci 23:361–367.  https://doi.org/10.1007/s10103-007-0494-2 Google Scholar
  100. 100.
    Schwartz C, Rühm A, Tonn J-C, Kreth S, Kreth F-W (2015) Surg-25interstitial photodynamic therapy of de-novo glioblastoma multiforme who IV. Neuro-Oncology 17:v219–v220.  https://doi.org/10.1093/neuonc/nov235.25 Google Scholar
  101. 101.
    Dupont C, Vermandel M, Leroy HA, Quidet M, Lecomte F, Delhem N, Mordon S, Reyns N (2018) INtraoperative photoDYnamic therapy for glioblastomas: study protocol for a phase I clinical trial. Neurosurgery  https://doi.org/10.1093/neuros/nyy324 Google Scholar
  102. 102.
    Vermandel M, Dupont C, Quidet M, Lecomte F, Lerhun E, Mordon S, Betrouni N, Reyns N (2017) Set-up of the first pilot study on intraopertive 5-ALA PDT: INDYGO trial. Photodiagn Photodyn Ther 17:A21.  https://doi.org/10.1016/j.pdpdt.2017.01.048 Google Scholar
  103. 103.
    Krishnamurthy S, Powers SK, Witmer P, Brown T (2000) Optimal light dose for interstitial photodynamic therapy in treatment for malignant brain tumors. Lasers Surg Med 27:224–234Google Scholar
  104. 104.
    Anderson I, Naylor T, McKinlay J, Sivakumar G (2015) Intra-operative acidosis during 5-aminolevulinic acid assisted glioma resection. BMJ Case Reports 2015: bcr2014207904  https://doi.org/10.1136/bcr-2014-207904 Google Scholar
  105. 105.
    Chung IW, Eljamel S (2013) Risk factors for developing oral 5-aminolevulinic acid-induced side effects in patients undergoing fluorescence guided resection. Photodiagn Photodyn Ther 10:362–367.  https://doi.org/10.1016/j.pdpdt.2013.03.007 Google Scholar
  106. 106.
    Quon H, Grossman CE, King RL, Putt M, Donaldson K, Kricka L, Finlay J, Zhu T, Dimofte A, Malloy K, Cengel KA, Busch TM (2010) Interference with the Jaffe method for creatinine following 5-aminolevulinic acid administration. Photodiagn Photodyn Ther 7:268–274.  https://doi.org/10.1016/j.pdpdt.2010.07.008 Google Scholar
  107. 107.
    Webber J, Kessel D, Fromm D (1997) Side effects and photosensitization of human tissues after aminolevulinic acid. J Surg Res 68:31–37.  https://doi.org/10.1006/jsre.1997.5004 Google Scholar

Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  1. 1.Icahn School of Medicine at Mount SinaiNew YorkUSA
  2. 2.Brain Tumor Nanotechnology Laboratory, Department of Neurosurgery, Tisch Cancer InstituteIcahn School of Medicine at Mount SinaiNew YorkUSA
  3. 3.Department of NeurosurgeryMount Sinai Beth IsraelNew YorkUSA
  4. 4.Department of Radiation Oncology, Perelman School of MedicineUniversity of PennsylvaniaPhiladelphiaUSA
  5. 5.Laser-Research Laboratory, LIFE-Center, Department of UrologyUniversity Hospital of MunichMunichGermany

Personalised recommendations