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Proceedings Paper

Potentiation of ALA-PDT antitumor activity in mice using topical DMXAA
Author(s): Allison Marrero; Ulas Sunar; Theresa Sands; Allan Oseroff; David Bellnier
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Paper 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.

Paper Details

Date Published: 13 July 2009
PDF: 7 pages
Proc. SPIE 7380, Photodynamic Therapy: Back to the Future, 738071 (13 July 2009); doi: 10.1117/12.829644
Show Author Affiliations
Allison Marrero, Roswell Park Cancer Institute (United States)
Ulas Sunar, Roswell Park Cancer Institute (United States)
Theresa Sands, Roswell Park Cancer Institute (United States)
Allan Oseroff, Roswell Park Cancer Institute (United States)
David Bellnier, Roswell Park Cancer Institute (United States)

Published in SPIE Proceedings Vol. 7380:
Photodynamic Therapy: Back to the Future
David H. Kessel, Editor(s)

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