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.
Photodynamic therapy (PDT) using topical aminolevulinic acid (ALA) is currently used as a clinical treatment for
nonmelanoma skin cancers. In order to optimize PDT treatment, vascular shutdown early in treatment must be identified
and prevented. This is especially important for topical ALA PDT where vascular shutdown is only temporary and is not
a primary method of cell death. Shutdown in vasculature would limit the delivery of oxygen which is necessary for
effective PDT treatment. Diffuse correlation spectroscopy (DCS) was used to monitor relative blood flow changes in
Balb/C mice undergoing PDT at fluence rates of 10mW/cm2 and 75mW/cm2 for colon-26 tumors implanted
intradermally. DCS is a preferable method to monitor the blood flow during PDT of lesions due to its ability to be used
noninvasively throughout treatment, returning data from differing depths of tissue. Photobleaching of the photosensitizer
was also monitored during treatment as an indirect manner of monitoring singlet oxygen production. In this paper, we
show the conditions that cause vascular shutdown in our tumor model and its effects on the photobleaching rate.
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