Potentiation of ALA-PDT antitumor activity in mice using topical DMXAA

Allison Marrero; Ulas Sunar; Theresa Sands; Allan Oseroff; David Bellnier

doi:10.1117/12.829644

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13 July 2009 Potentiation of ALA-PDT antitumor activity in mice using topical DMXAA

Allison Marrero; Ulas Sunar; Theresa Sands; Allan Oseroff; David Bellnier

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Proceedings Volume 7380, Photodynamic Therapy: Back to the Future; 738071 (2009) https://doi.org/10.1117/12.829644
Event: 12th World Congress of the International Photodynamic Association, 2009, Seattle, Washington, United States

Abstract

Photodynamic treatment of subcutaneously implanted Colon 26 tumors in BALB/c mice using the aminolevulinic acid (ALA)-induced photosensitizer protoporphyrin IX (PpIX) was shown to be enhanced by the addition of the vascular disrupting agent 5,6-Dimethylxanthenone-4-acetic-acid (DMXAA; Novartis ASA404). DMXAA increases vascular permeability and decreases blood flow in both murine and human tumors. Sufficiently high parenteral DMXAA doses can lead to tumor collapse and necrosis. We have previously reported marked enhancement of antitumor activity when PDT, using either Photofrin or HPPH, is combined with low-dose intraperitoneal DMXAA. We now describe the first attempt to combine topically-applied DMXAA with PDT. For this, DMXAA was applied two hours before PpIX-activating light delivery. PDT with ALA-PDT alone (ALA 20%; 80 J/cm² delivered at 75 mW/cm²) caused a 39% decrease in tumor volume compared to unirradiated controls. Addition of topical DMXAA to ALA-PDT resulted in a 74% reduction in tumor volume. Diffuse correlation spectroscopy (DCS), a non-invasive blood flow imaging method, is being used to understand the mechanism of this effect and to aid in the proper design of the therapy. For instance, our most recent DCS data suggests that the 2-hour interval between the DMXAA and light applications may not be optimum. This preliminary study suggests a potential role for topical DMXAA in combination with PDT for dermatologic tumors.

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Allison Marrero, Ulas Sunar, Theresa Sands, Allan Oseroff, and David Bellnier "Potentiation of ALA-PDT antitumor activity in mice using topical DMXAA", Proc. SPIE 7380, Photodynamic Therapy: Back to the Future, 738071 (13 July 2009); https://doi.org/10.1117/12.829644

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