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Proceedings Paper

Metronomic photodynamic therapy (mPDT): concepts and technical feasibility in brain tumor
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Paper Abstract

The concept of metronomic photodynamic therapy (mPDT) is presented, in which both the photosensitizer and light are delivered continuously at low rates over extended periods in order to increase selective tumor cell kill through apoptosis. The focus of the present work is on mPDT treatment of malignant brain tumors, in which selectivity between damage to tumor cells versus normal brain tissue is critical. Previous studies have shown that low-dose PDT using aminolevulinic acid (ALA)-induced protoporphyrin IX (PpIX) can induce apoptosis in tumor cells without causing necrosis in either tumor or normal brain tissue or apoptosis in the latter. In order to produce enough tumor cell kill to be an effective therapy, multiple PDT treatments, such as hyperfractionation or metronomic delivery, are likely requried, based on the levels of apoptosis achieved and model calculations of tumor growth rates. mPDT poses two substantial technical challenges: extended delivery of ALA and implantation of interstitial devices for extended light delivery while allowing free movement. In rat models ALA administration via the drinking water has been accomplished at significant doses for up to 10 days, and ex vivo spectrofluorimetry of tumore, normal brain and other tissues post mortem demonstrates a 3-4 increase in the tumor-to-brain concentration of PpIX, without toxicity. Prototype light sources and delivery devices are also shown to be practical, either using a laser diode or light emitting diode (LED) coupled to an implanted optical fiber in the case of the rat model or a directly-implanted LED in rabbits. The combined delivery of both drug and light over an extended period, with survival of the animals, is demonstrated. Preliminary evidence of selective apoptosis of tumor under these conditions is presented.

Paper Details

Date Published: 13 June 2003
PDF: 9 pages
Proc. SPIE 4952, Optical Methods for Tumor Treatment and Detection: Mechanisms and Techniques in Photodynamic Therapy XII, (13 June 2003); doi: 10.1117/12.479435
Show Author Affiliations
Brian C. Wilson, Ontario Cancer Institute/Univ. Health Network (Canada)
Univ. of Toronto (Canada)
Stuart K. Bisland, Ontario Cancer Institute/Univ. Health Network (Canada)
Arjen Bogaards, Ontario Cancer Institute/Univ. Health Network (Canada)
Annie Lin, Ontario Cancer Institute/Univ. Health Network (Canada)
Eduardo H. Moriyama, Ontario Cancer Institute/Univ. Health Network (Canada)
Kai Zhang, Photonics Research Ontario (Canada)
Lothar D. Lilge, Ontario Cancer Institute/Univ. Health Network (Canada)
Univ. of Toronto (Canada)


Published in SPIE Proceedings Vol. 4952:
Optical Methods for Tumor Treatment and Detection: Mechanisms and Techniques in Photodynamic Therapy XII
David Kessel, Editor(s)

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