Photodynamic therapy of established prostatic adenocarcinoma with TOOKAD: A biphasic apparent diffusion coefficient change as potential early MRI response marker

Vicki Plaks, Natalia Koudinova, Uri Nevo, Jehonathan H. Pinthus, Hannah Kanety, Zelig Eshhar, Jacob Ramon, Avigdor Scherz, Michal Neeman, Yoram Salomon*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

46 Scopus citations

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.

Original languageEnglish
Pages (from-to)224-233
Number of pages10
JournalNeoplasia
Volume6
Issue number3
DOIs
StatePublished - 2004

Funding

FundersFunder number
Wilner Foundation for Vascular Biology

    Keywords

    • Cell spheroid
    • Diffusion MRI
    • Human prostate adenocarcinoma
    • Photodynamic therapy
    • TOOKAD

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