Metronomic photodynamic therapy (mPDT) -- headlights to lead the way forward:  technical feasibility and rationale in brain tumor

Stuart L. Bisland; Lothar D. Lilge; Annie Lin; Arjen Bogaards; Brian C. Wilson

doi:10.1117/12.543443

15 December 2003 Metronomic photodynamic therapy (mPDT) -- headlights to lead the way forward: technical feasibility and rationale in brain tumor

Stuart L. Bisland, Lothar D. Lilge, Annie Lin, Arjen Bogaards, Brian C. Wilson

Author Affiliations +

Proceedings Volume 5260, Applications of Photonic Technology 6; (2003) https://doi.org/10.1117/12.543443
Event: Applications of Photonic Technology, 2003, Quebec City, Québec, Canada

Abstract

The concept of metronomic photodynamic therapy (mPDT) is presented, in which both the photosensitizer and light are deliverd 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 taht low-dose PDT using aminolevulinic acid (ALA)-induced protoporphyrin IX (PpIX) can induce apoptosis in tumor cells within causing nectrosis in either tumor or normal brain tissue or apoptosis in teh 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 required, 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 ALAL administration via the drinking water has been accomplished at significant doesse (up to 10 times therapeutic dose) for up to 10 days, and ex vivo spectrofluorimetry of tumor, 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 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 animls, is demonstrated. Preliminary evidence of selective aopotosis of tumor under these conditions is presented.

Citation Download Citation

Stuart L. Bisland, Lothar D. Lilge, Annie Lin, Arjen Bogaards, and Brian C. Wilson "Metronomic photodynamic therapy (mPDT) -- headlights to lead the way forward: technical feasibility and rationale in brain tumor", Proc. SPIE 5260, Applications of Photonic Technology 6, (15 December 2003); https://doi.org/10.1117/12.543443

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