Blood flow dynamics during local photoreaction in a head and neck tumor model

Abstract

We have applied continuous blood flow dynamics, quantified with diffuse correlation spectroscopy (DCS), in investigating photodynamic therapy (PDT) induced local photoreaction in a head and neck tumor model. Photoclor (0.47 μmol/kg) was intravenously administered 24 h before PDT. Two types of fluence rates were implemented: Low fluence rate (14 mW/cm2) and high fluence rate (75 mW/cm2). The total delivered fluence was 100 J/cm2 for both types. We observed that PDT induced substantial vascular shut down in both types. While the shutdown was persistent in tumors exposed to low fluence rate PDT, the shutdown was transient in tumors exposed to high fluence PDT. Loss of microvascular structures was confirmed by the microscopic analyses of tumor section following immunostaining for CD31. Blood flow dynamics related metrics were also strongly correlated with crosslinking of STAT3, a molecular marker of photoreaction. STAT3 analysis indicated that low fluence rate yields a substantially higher photoreaction, and thus, a more effective PDT. Our results indicate that non-invasive blood flow measurements can monitor the efficacy of PDT in real-time and potentially provide a feedback for its optimization.