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

Daniel J Rohrbach,Erin C Tracy,Ulas Sunar,Heinz Baumann,Jessica Walker

doi:10.3389/fphy.2015.00013

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 hour 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 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 noninvasive blood flow measurements can monitor the efficacy of PDT in real-time and potentially provide a feedback for its optimization.

Highlights

Head and neck tumors in the oral cavity are the sixth most common cancer in the world [1]
We show that blood flow dynamics assessed by continuous diffuse correlation spectroscopy (DCS) measurements can inform about photodynamic therapy (PDT)-induced changes non-invasively, suggesting real-time blood flow monitoring would allow for PDT optimization in clinical settings
Head and neck tumors in mice treated with HPPH-PDT showed several characteristic features of blood flow dynamics during light exposure

Summary

Introduction

Head and neck tumors in the oral cavity are the sixth most common cancer in the world [1]. Chemotherapy showed high relapse rates and toxicities. Any alternative therapy must balance therapeutic effectiveness with treatment toxicity. Such an alternative is provided by photodynamic therapy (PDT), which relies on the optimal application of a tumor-localized photosensitizing drug, oxygen, and light. PDT is a local therapy with superior healing without cumulative side effects, and can be repeated several times [3]. It is well suited for treatment of head and neck cancers with multiple tumor foci or widespread diseases (e.g., leukoplakia or invasive carcinoma in the oral cavity) [4]. PDT responses can vary from ∼90 to ∼45% depending

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Conclusion