title: Photodynamic therapy of established prostatic adenocarcinoma with TOOKAD: a biphasic apparent diffusion coefficient change as potential early MRI response marker.
abstract: 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.
authors.affiliation: Department of Biological Regulation, The Weizmann Institute of Science, Rehovot 76100, Israel.
authors.forename: Vicki
authors.initials: V
authors.lastname: Plaks
authors.forename: Natalia
authors.initials: N
authors.lastname: Koudinova
authors.forename: Uri
authors.initials: U
authors.lastname: Nevo
authors.forename: Jehonathan H
authors.initials: JH
authors.lastname: Pinthus
authors.forename: Hannah
authors.initials: H
authors.lastname: Kanety
authors.forename: Zelig
authors.initials: Z
authors.lastname: Eshhar
authors.forename: Jacob
authors.initials: J
authors.lastname: Ramon
authors.forename: Avigdor
authors.initials: A
authors.lastname: Scherz
authors.forename: Michal
authors.initials: M
authors.lastname: Neeman
authors.forename: Yoram
authors.initials: Y
authors.lastname: Salomon
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D000818:Animals; D001429:Bacteriochlorophylls / Q000627:therapeutic use*; D004058:Diffusion; D038524:Diffusion Magnetic Resonance Imaging / Q000379:methods*; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D051379:Mice; D008819:Mice, Nude; D010778:Photochemotherapy; D017319:Photosensitizing Agents / Q000627:therapeutic use*; D011471:Prostatic Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D016896:Treatment Outcome; D014407:Tumor Cells, Cultured; D023041:Xenograft Model Antitumor Assays
chemical_list: D001429:Bacteriochlorophylls; D017319:Photosensitizing Agents; C456120:palladium-bacteriopheophorbide