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Vol. 30, No. 5, 1999
Issue release date: May 1999
Pediatr Neurosurg 1999;30:225–231

Preclinical Evaluation of Benzoporphyrin Derivative Combined with a Light-Emitting Diode Array for Photodynamic Therapy of Brain Tumors

Schmidt M.H. · Reichert II K.W. · Ozker K. · Meyer G.A. · Donohoe D.L. · Bajic D.M. · Whelan N.T. · Whelan H.T.
Departments of aNeurosurgery, bNuclear Medicine, cNeurology and dPediatrics, Medical College of Wisconsin, Milwaukee, Wisc.; eNASA-Marshall Space Flight Center, Huntsville, Ala., USA

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Objective: The aim of this study was to investigate the second-generation photosensitizer benzoporphyrin derivative (BPD) and a novel light source applicator based on light-emitting diode (LED) technology for photodynamic therapy (PDT) of brain tumors. Methods: We used a canine model to investigate normal brain stem toxicity. Twenty-one canines underwent posterior fossa craniectomies followed by PDT with BPD. These animals were compared to light only and BPD control. In addition, we investigated the ability of BPD and LED to cause inhibition of cell growth in canine glioma and human glioma cell lines, in vitro. The biodistribution of BPD labeled with 111In-BPD in mice with subcutaneous and intracerebral gliomas and canines with brain tumors was studied. Results: The in vivo canine study resulted in a maximal tolerated dose of 0.75 mg/kg of BPD and 100 J/cm2 of LED light for normal brain tissue. The in vitro study demonstrated 50% growth inhibition for canine and human glioma cell lines of 10 and 4 ng/ml, respectively. The mucine study using 111In-BPD showed a tumor to normal tissue ratio of 12:1 for intracerebral tumors and 3.3:1 for subcutaneous tumors. Nuclear scans of canines with brain tumors showed uptake into tumors to be maximal from 3 to 5 h. Conclusion: Our study supports that BPD and LED light sources when used at appropriate drug and light doses limit normal brain tissue toxicity at doses that can cause significant glioma cell toxicity in vitro. In addition, there is higher BPD uptake in brain tumors as compared to normal brain in a mouse glioma model. These findings make BPD a potential new-generation photosensitizer for the treatment of childhood posterior fossa tumors as well as other malignant cerebral pathology.

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Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in goverment regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
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  1. Ji Y, Walstad D, Brown JT, Powers SK: Improved survival from intracavitary photodynamic therapy of rat glioma. Photochem Photobiol 1992;56:385–390.

    External Resources

  2. Kaye AH, Morstyn G, Brownbill D: Adjuvant high-dose photoradiation therapy in the treatment of cerebral glioma: A phase 1–2 study. J Neurosurg 1987;67:500–505.
  3. Kostron H, Weiser G, Fritsch E, Grunert V: Photodynamic therapy of malignant brain tumors: Clinical and neuropathological results. Photochem Photobiol 1987;46:937–943.

    External Resources

  4. Laws ER Jr, Cortese DA, Kinsey JH, Eagan RT, Anderson RE: Photoradiation therapy in the treatment of malignant brain tumors: A phase I (feasibility) study. Neurosurgery 1981;9:672–678.
  5. Muller PJ, Wilson BC: Photodynamic therapy of malignant brain tumours. Can J Neurol Sci 1990;17:193–198.
  6. Powers SK, Cush SS, Walstad DL, Kwock L: Stereotactic intratumoral photodynamic therapy for recurrent malignant brain tumors. Neurosurgery 1991;29:688–695.
  7. Origitano TC, Caron MJ, Reichman OH: Photodynamic therapy for intracranial neoplasms. Literature review and institutional experience. Mol Chem Neuropathol 1994;21:337–352.

    External Resources

  8. Whelan HT, Schmidt MH, Segura AD, McAuliffe TL, Bajic DM, Murray KJ, Moulder JE, Strother DR, Thomas JP, Meyer GA: The role of photodynamic therapy in posterior fossa brain tumors: A preclinical study in a canine glioma model. J Neurosurg 1993;79:562–568.
  9. Muller PJ, Wilson BC: Photodynamic therapy for recurrent supratentorial gliomas. Semin Surg Oncol 1995;11:346–354.

    External Resources

  10. Popovoc EA, Kaye AH, Hill JS: Photodynamic therapy of brain tumors. Semin Surg Oncol 1995;11:335–345.
  11. Kostron H, Obwegeser A, Jakober R: Photodynamic therapy in neurosurgery: A review. J Photochem Photobiol B 1996;36:157–168.
  12. Henderson BW, Dougherty TJ: How does photodynamic therapy work. Photochem Photobiol 1992;55:145–157.
  13. Hill AH, Kaye AH, Sawyer WH, Morstyn G, Megison PD, Stylli S: Selective uptake of hematoporphyrin derivative into human cerebral glioma. Neurosurgery 1990;26:248–254.
  14. Whelan HT, Kras LH, Ozker K, Bajic D, Schmidt MH, Liu Y, Trembath LA, Uzum F, Meyer GA, Segura AD, Collier BD: Selective incorportation of 111In-labeled PHOTOFRIN by glioma tissue in vivo. J Neurooncol 1994;22:7–13.
  15. Schmidt MH: Intraoperative photodynamic therapy in a posterior fossa brain tumor model. Medical School Thesis, 1994.
  16. Schmidt MH, Bajic DM, Reichert KW, Martin TS, Meyer GA, Whelan HT: Light-emitting diodes as a light source for intraoperative photodynamic therapy. Neurosurgery 1996;38:552–556.

    External Resources

  17. Aveline B, Hasan T, Redmond RW: Photophysical and photosensitizing properties of benzoporphyrin derivative monoacid ring A (BPD-MA)*. Photochem Photobiol 1994;59:328–335.
  18. Barta DJ, Tibbitts TW, Bula RJ, Morrow RC: Evaluation of light-emitting diode characteristics for a spaced-based plant irradiation source. Adv Space Res 1992;12:141–149.
  19. Bula RJ, Morrow RC, Tibbitts TW, Barta DJ, Ignatius RW, Martin TS: Light-emitting diodes as a radiation source for plants. Hort Sci 1991;26:203–205.

    External Resources

  20. Tennessen DJ, Singsaas EL, Sharkey TD: Light-emitting diodes as a light source for photosynthesis research. Photosynth Res 1994;39:85–92.
  21. Whelan HT, Pledger WJ, Maciunas RJ, Galloway RL Jr, Whetsell SO Jr, Moses HL: Growth factors in the tumorigenicity of a brain tumor cell line. Pediatr Neurol 1989;5:271–279.
  22. Whelan HT, Przybylski C, Bajic DM, Schmidt MH: Intracellular growth factor metabolism in proliferation of a brain tumor cell line. J Neurooncol 1993;15:243–250.
  23. Collins JM, Zaharko DS, Dedrick RL, Chabner BA: Potential roles for preclinical pharmacology in phase I clinical trials. Cancer Treat Rep 1986;70:73–80.

    External Resources

  24. Goldsmith MA, Slavik M, Carter SK: Quantitative prediction of drug toxicity in humans from toxicology in small and large animals. Cancer Res 1975;35:1354–1364.

    External Resources

  25. Kassis AI, Taube RA: Efficient radiolabeling of mammalian cells using In-111-tagged liposomes. Nucl Med Biol 1987;14:33–35.
  26. Awasthi V, Boins B, Klipper R, Loredo R, Korvick D, Phillips WT: Imaging experimental osteomyelitis using radiolabeled liposomes. J Nucl Med 1998;39:1089–1094.
  27. Whelan HT, Clanton JA, Wilson RE, Tulipan NB: Comparison of CT and MRI brain tumor imaging using a canine glioma model. Pediatr Neurol 1988;4:279–283.
  28. Salcman M: Glioblastoma and malignant astrocytoma; in Kaye AH, Laws ER (eds): Brain Tumors. Edinburgh, Churchill Livingstone, 1995, 449–477.
  29. Whelan HT, Krouwer HG, Schmidt MH, Reichert KW, Kovnar EH: Current therapy and new perspectives in the treatment of medulloblastoma. Pediatr Neurol 1998;18:103–115.

    External Resources

  30. Muller PJ, Wilson BC: An update on the penetration depth of 630 nm light in normal and malignant human brain tissue in vivo. Phys Med Biol 1986;31:1295–1297.
  31. Muller PJ, Wilson BC: Photodynamic therapy of malignant primary brain tumors: Clinical effects, post-operative ICP, and light penetration of the brain. Photochem Photobiol 1987;46:929–935.
  32. Dougherty TJ, Wieshaupt KR, Boyle DG: Photodynamic sensitizers; in deVita VT Jr, Hellman S, Rosenberg SA (eds): ‘Cancer’ Principles and Practice of Oncology. Philadelphia, Lippincott, 1985, vol 2, pp 2272–2279.
  33. Eggert HR, Blazek V: Optical properties of normal human brain tissue, meninges, and brain tumors in the spectral range of 200 to 900 nm. Neurosurgery 1987;21:459–464.

    External Resources

  34. Khalifa A, Dodds D, Rampling R, Paterson J, Murray T: Liposomal distribution in malignant glioma: Possibilities of therapy. Nucl Med Commun 1997;18:17–23.

    External Resources

  35. Gennuso R, Spigelman MK, Chinol M, Zappula RA, Nieves J, Vallabhajosula S, Paciucci A, Goldsmith SJ, Holland JF: Effect of blood brain barrier and blood tumor barrier modification on central nervous system liposomal uptake. Cancer Invest 1993;11:118–128.

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