Laser speckle imaging is a technique that has been developed to non-invasively monitor in vivo blood flow dynamics and
vascular structure, at high spatial and temporal resolution. It can record the full-field spatio-temporal characteristics of
microcirculation and has therefore, often been used to study the blood flow in tumors after photodynamic therapy (PDT).
Yet, there is a paucity of reports on real-time laser speckle imaging (RTLSI) during PDT. Vascular-targeted
photodynamic therapy (VTP) with WST11, a water-soluble bacteriochlorophyll derivative, achieves tumor ablation
through rapid occlusion of the tumor vasculature followed by a cascade of events that actively kill the tumor cells.
WST11-VTP has been already approved for treatment of early/intermediate prostate cancer at a certain drug dose, time
and intensity of illumination. Application to other cancers may require different light dosage. However, incomplete
vascular occlusion at lower light dose may result in cancer cell survival and tumor relapse while excessive light dose
may lead to toxicity of nearby healthy tissues. Here we provide evidence for the feasibility of concomitant RTLSI of the
blood flow dynamics in the tumor and surrounding normal tissues during and after WST11-VTP. Fast decrease in the
blood flow is followed by partial mild reperfusion and a complete flow arrest within the tumor by the end of
illumination. While the primary occlusion of the tumor feeding arteries and draining veins agrees with previous data
published by our group, the late effects underscore the significance of light dose control to minimize normal tissue
impairment. In conclusion- RTSLI application should allow to optimize VTP efficacy vs toxicity in both the preclinical
and clinical arenas.
It is increasingly evident that the most effective cancer treatments will involve interactive regimens that target multiple non-overlapping pathways, preferably such that each component enhances the others to improve outcomes while minimizing systemic toxicities. Toward this goal, we developed a combination of photodynamic therapy and irinotecan, which mechanistically cooperate with each other, beyond their individual tumor destruction pathways, to cause synergistic reduction in orthotopic pancreatic tumor burden. A three-way mechanistic basis of the observed the synergism will be discussed: (i) PDT downregulates drug efflux transporters to increase intracellular irinotecan levels. (ii) Irinotecan reduces the expression of hypoxia-induced marker, which is upregulated by PDT. (iii) PDT downregulates irinotecan-induced survivin expression to amplify the apoptotic and anti-proliferative effects. The clinical translation potential of the combination will also be highlighted.
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