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Interstitial Doppler Optical Coherence Tomography as a Local Tumor Necrosis Predictor in Photodynamic Therapy of Prostatic Carcinoma: An In vivo Study

¹ Department of Medical Biophysics and ² Radiation Oncology, University of Toronto, ³ Ontario Cancer Institute/University Health Network, ⁴ Department Electrical and Computer Engineering, Ryerson University, and ⁵ Imaging Research, Sunnybrook Health Sciences Center, Toronto, Canada

Requests for reprints: Brian C. Wilson, Ontario Cancer Institute/University Health Network, Department of Medical Biophysics, University of Toronto, 610 University Avenue, Toronto, ON, Canada M5G 2M9. Phone: 416-946-4501, ext. 2952; Fax: 416-946-6529; E-mail: wilson{at}uhnres.utoronto.ca.

Key Words: photodynamic therapy • Doppler optical coherence tomography • blood flow • cancer • microvasculature

We have tested the feasibility of real-time localized blood flow measurements, obtained with interstitial (IS) Doppler optical coherence tomography (DOCT), to predict photodynamic therapy (PDT)-induced tumor necrosis deep within solid Dunning rat prostate tumors. IS-DOCT was used to quantify the PDT-induced microvascular shutdown rate in s.c. Dunning prostate tumors (n = 28). Photofrin (12.5 mg/kg) was administered 20 to 24 hours before tumor irradiation, with 635 nm surface irradiance of 8 to 133 mWcm^–2 for 25 minutes. High frequency ultrasound and calipers were used to measure the thickness of the skin covering the tumor and the location of the echogenic IS probe within it. A two-layer Monte Carlo model was used to calculate subsurface fluence rates within the IS-DOCT region of interest (ROI). Treatment efficacy was estimated by percent tumor necrosis within the ROI, as quantified by H&E staining, and correlated to the measured microvascular shutdown rate during PDT treatment. IS-DOCT measured significant PDT-induced vascular shutdown within the ROI in all tumors. A strong relationship (R² = 0.723) exists between the percent tumor necrosis at 24 hours posttreatment and the vascular shutdown rate: slower shutdown corresponded to higher treatment efficacy, i.e., more necrosis. Controls (needle + light, no drug, n = 3) showed minimal microvascular changes or necrosis (4% ± 1%). This study has correlated a biological end point with a direct and localized measurement of PDT-induced microvascular changes, suggesting a potential clinical role of on-line, real-time microvascular monitoring for optimizing treatment efficacy in individual patients. [Cancer Res 2008;68(23):9987–95]