Early assessment of tumor response to photodynamic therapy using combined diffuse optical and diffuse correlation spectroscopy to predict treatment outcome

// Patricia Thong 1 , Kijoon Lee 2, 4, 6 , Hui-Jin Toh 1 , Jing Dong 2, 4, 5 , Chuan-Sia Tee 1 , Kar-Perng Low 1 , Pui-Haan Chang 1 , Ramaswamy Bhuvaneswari 1 , Ngian-Chye Tan 3 , Khee-Chee Soo 1 1 Division of Medical Sciences, National Cancer Centre, Singapore 2 Division of Bioengineering, School of Chemical and Biomedical Engineering, Nanyang Technological University, Singapore 3 Division of Surgical Oncology, National Cancer Centre, Singapore 4 Nanyang Technological University, Singapore 5 Current address: Harvard Medical School and Wellman Center for Photomedicine, Massachusetts General Hospital, Boston, MA, USA 6 Current address: Daegu Gyeongbuk Institute of Science and Technology, Daegu, Korea Correspondence to: Khee-Chee Soo, email: admskc@nccs.com.sg Keywords: photodynamic therapy, treatment response monitoring, optical spectroscopy, tissue oxygenation, relative blood flow Received: May 26, 2016      Accepted: January 16, 2017      Published: February 25, 2017 ABSTRACT Photodynamic therapy (PDT) of cancer involves the use of a photosensitizer that can be light-activated to eradicate tumors via direct cytotoxicity, damage to tumor vasculature and stimulating the body’s immune system. Treatment outcome may vary between individuals even under the same regime; therefore a non-invasive tumor response monitoring system will be useful for personalization of the treatment protocol. We present the combined use of diffuse optical spectroscopy (DOS) and diffuse correlation spectroscopy (DCS) to provide early assessment of tumor response. The relative tissue oxygen saturation (rStO2) and relative blood flow (rBF) in tumors were measured using DOS and DCS respectively before and after PDT with reference to baseline values in a mouse model. In complete responders, PDT-induced decreases in both rStO2 and rBF levels were observed at 3 h post-PDT and the rBF remained low until 48 h post-PDT. Recovery of these parameters to baseline values was observed around 2 weeks after PDT. In partial responders, the rStO2 and rBF levels also decreased at 3 h post PDT, however the rBF values returned toward baseline values earlier at 24 h post-PDT. In contrast, the rStO2 and rBF readings in control tumors showed fluctuations above the baseline values within the first 48 h. Therefore tumor response can be predicted at 3 to 48 h post-PDT. Recovery or sustained decreases in the rBF at 48 h post-PDT corresponded to long-term tumor control. Diffuse optical measurements can thus facilitate early assessment of tumor response. This approach can enable physicians to personalize PDT treatment regimens for best outcomes.