Early assessment of tumor response to photodynamic therapy using combined diffuse optical and diffuse correlation spectroscopy to predict treatment outcome
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Patricia S.P. Thong1, Kijoon Lee2,4,6, Hui-Jin Toh1, Jing Dong2,4,5, Chuan-Sia Tee1, Kar-Perng Low1, Pui-Haan Chang1, Ramaswamy Bhuvaneswari1, Ngian-Chye Tan3, Khee-Chee Soo1
1Division of Medical Sciences, National Cancer Centre, Singapore
2Division of Bioengineering, School of Chemical and Biomedical Engineering, Nanyang Technological University, Singapore
3Division of Surgical Oncology, National Cancer Centre, Singapore
4Nanyang Technological University, Singapore
5Current address: Harvard Medical School and Wellman Center for Photomedicine, Massachusetts General Hospital, Boston, MA, USA
6Current address: Daegu Gyeongbuk Institute of Science and Technology, Daegu, Korea
Khee-Chee Soo, email: [email protected]
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
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.
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