title: Interstitial Doppler optical coherence tomography as a local tumor necrosis predictor in photodynamic therapy of prostatic carcinoma: an in vivo study.
abstract: 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.
authors.affiliation: Department of Medical Biophysics and Radiation Oncology, University of Toronto, Ontario Cancer Institute/University Health Network, Toronto, Canada.
authors.forename: Beau A
authors.initials: BA
authors.lastname: Standish
authors.forename: Kenneth K C
authors.initials: KK
authors.lastname: Lee
authors.forename: Xiao
authors.initials: X
authors.lastname: Jin
authors.forename: Adrian
authors.initials: A
authors.lastname: Mariampillai
authors.forename: Nigel R
authors.initials: NR
authors.lastname: Munce
authors.forename: Michael F G
authors.initials: MF
authors.lastname: Wood
authors.forename: Brian C
authors.initials: BC
authors.lastname: Wilson
authors.forename: I Alex
authors.initials: IA
authors.lastname: Vitkin
authors.forename: Victor X D
authors.initials: VX
authors.lastname: Yang
mesh_terms: D000818:Animals; D017323:Dihematoporphyrin Ether; D007090:Image Interpretation, Computer-Assisted; D008297:Male; D008954:Models, Biological; D009010:Monte Carlo Method; D009336:Necrosis; D010778:Photochemotherapy; D011471:Prostatic Neoplasms / Q000098:blood supply* / Q000000981:diagnostic imaging / Q000188:drug therapy* / Q000473:pathology; D051381:Rats; D041623:Tomography, Optical Coherence / Q000295:instrumentation / Q000379:methods*; D014463:Ultrasonography; D023041:Xenograft Model Antitumor Assays
chemical_list: D017323:Dihematoporphyrin Ether