The use of diffuse optical spectroscopy and diffuse correlation spectroscopy system for monitoring of tumor response to photodynamic therapy

Abstract

Photodynamic therapy (PDT) of cancer works via direct cytotoxicity, causing damage to tumor vasculature and stimulating the body’s anti-tumor immune response. PDT outcome depends on the parameters used; therefore an in vivo tumor response monitoring system is useful for optimization of the treatment protocol. The combined use of diffuse optical spectroscopy and diffuse correlation spectroscopy allows us to measure the tissue oxygen saturation (StO₂) and relative blood flow (rBF) in tumors. These parameters were measured before and after PDT in mouse tumor models and were calculated as ratios relative to the baseline in each tumor (rStO₂ and rBF). Readings were also measured in drugonly control tumors. In responders (mice with tumor eradication), significant PDT-induced decreases in both rStO₂ and rBF levels were observed at 3h post-PDT. The rStO₂ and rBF readings in these mice remained low until 48h post-PDT, with recovery of these parameters to baseline values observed 2 weeks after PDT. In non-responders (mice with partial or no response), the rStO₂ and rBF levels decreased less sharply at 3h post-PDT, and the rBF values returned toward baseline values at 48h post-PDT. By comparison, the rStO₂and rBF readings in drug-only control tumors showed only fluctuations about the baseline values. Thus tumor response can be predicted as early as 3h post-PDT. Recovery or sustained decreases in rStO₂ and rBF up till 48h post-PDT were correlated to long-term tumor control. Diffuse optical measurements can thus facilitate early assessment of tumor response to PDT to aid in treatment planning.