TY - JOUR
T1 - Photodynamic therapy of established prostatic adenocarcinoma with TOOKAD
T2 - A biphasic apparent diffusion coefficient change as potential early MRI response marker
AU - Plaks, Vicki
AU - Koudinova, Natalia
AU - Nevo, Uri
AU - Pinthus, Jehonathan H.
AU - Kanety, Hannah
AU - Eshhar, Zelig
AU - Ramon, Jacob
AU - Scherz, Avigdor
AU - Neeman, Michal
AU - Salomon, Yoram
N1 - Funding Information:
Abbreviations: ADC, apparent diffusion coefficient; DW, diffusion-weighted; MRI, magnetic resonance imaging; ECS, extracellular space; HNE, 4-hydroxy-2-nonenal; LPO, lipid peroxidation; PC, prostate cancer; PDT, photodynamic therapy; ROS, reactive oxygen species; WISH-PC14, Weizmann Institute Sheba Hospital prostate cancer 14; SCCP, small cell carcinoma of the prostate; PI, propidium iodide; ROI, region of interest Address all correspondence to: Prof. Yoram Salomon, Department of Biological Regulation, The Weizmann Institute of Science, Rehovot 76100, Israel. E-mail: [email protected] 1This study is in partial fulfillment of the MSc thesis of V.P. for the Feinberg Graduate School, The Weizmann Institute of Science. Y.S. is the incumbent of the Tillie and Charles Lubin Professorial Chair in Biochemical Endocrinology. A.S. is the incumbent of the Robert and Yadele Sklare Professional Chair in Biochemistry. This study was supported, in part, by the Wilner Foundation for Vascular Biology and by STEBA BIOTECH (Toussus-Le-Noble, France). Received 23 September 2003; Revised 2 December 2003; Accepted 3 December 2003.
PY - 2004
Y1 - 2004
N2 - The goal of this study was to examine the use of diffusion-weighted magnetic resonance imaging (DW-MRI) for the assessment of early progression of photodamage induced by Pd-bacteriopheophorbide (TOOKAD)-based photodynamic therapy (PDT). TOOKAD is a novel second-generation photosensitizer for PDT of solid tumors developed in our laboratory and presently under clinical trials for prostate cancer (PC) therapy. Using the subcutaneous human prostate adenocarcinoma WISH-PC14 xenografts in nude mice as a model, a unique biphasic change in the apparent diffusion coefficient (ADC) was observed within the first 24 hours post-PDT, with initial decrease followed by an increase in ADC. Using DW-MRI, this phenomenon enables the detection of successful tumor response to PDT within 7 hours posttreatment. This process was validated by direct, histological, and immunohistochemical examinations and also by evaluation of serum prostate-specific antigen (PSA) levels that decreased significantly already 7 hours posttreatment. In vitro studies of multicellular cell spheroids confirmed a PDT-induced decrease in ADC, suggesting that lipid peroxidation (LPO) significantly contributes to ADC decline observed after PDT. These results demonstrate that TOOKAD-based PDT successfully eradicates prostate adenocarcinoma xenografts and suggests DW-MRI to be useful for the detection of early tumor response and treatment outcome in the clinical setting.
AB - The goal of this study was to examine the use of diffusion-weighted magnetic resonance imaging (DW-MRI) for the assessment of early progression of photodamage induced by Pd-bacteriopheophorbide (TOOKAD)-based photodynamic therapy (PDT). TOOKAD is a novel second-generation photosensitizer for PDT of solid tumors developed in our laboratory and presently under clinical trials for prostate cancer (PC) therapy. Using the subcutaneous human prostate adenocarcinoma WISH-PC14 xenografts in nude mice as a model, a unique biphasic change in the apparent diffusion coefficient (ADC) was observed within the first 24 hours post-PDT, with initial decrease followed by an increase in ADC. Using DW-MRI, this phenomenon enables the detection of successful tumor response to PDT within 7 hours posttreatment. This process was validated by direct, histological, and immunohistochemical examinations and also by evaluation of serum prostate-specific antigen (PSA) levels that decreased significantly already 7 hours posttreatment. In vitro studies of multicellular cell spheroids confirmed a PDT-induced decrease in ADC, suggesting that lipid peroxidation (LPO) significantly contributes to ADC decline observed after PDT. These results demonstrate that TOOKAD-based PDT successfully eradicates prostate adenocarcinoma xenografts and suggests DW-MRI to be useful for the detection of early tumor response and treatment outcome in the clinical setting.
KW - Cell spheroid
KW - Diffusion MRI
KW - Human prostate adenocarcinoma
KW - Photodynamic therapy
KW - TOOKAD
UR - http://www.scopus.com/inward/record.url?scp=2442714993&partnerID=8YFLogxK
U2 - 10.1593/neo.3352
DO - 10.1593/neo.3352
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C2 - 15153334
AN - SCOPUS:2442714993
SN - 1522-8002
VL - 6
SP - 224
EP - 233
JO - Neoplasia
JF - Neoplasia
IS - 3
ER -