Photodynamic Therapy of Established Prostatic Adenocarcinoma with TOOKAD: A Biphasic Apparent Diffusion Coefficient Change as Potential Early MRI Response Marker

• Main Authors: Vicki Plaks, Natalia Koudinova, Uri Nevo, Jehonathan H. Pinthus, Hannah Kanety, Zelig Eshhar, Jacob Ramon, Avigdor Scherz, Michal Neeman, Yoram Salomon
• Format: Article
• Language: English
• Published: Elsevier 2004-05-01
• Series: Neoplasia: An International Journal for Oncology Research
• Subjects: Diffusion MRI; photodynamic therapy; human prostate adenocarcinoma; TOOKAD; cell spheroid
• Online Access: http://www.sciencedirect.com/science/article/pii/S1476558604800691

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, 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.