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Photodynamic therapy of established prostatic adenocarcinoma with TOOKAD: a biphasic apparent diffusion coefficient
Vicki Plaks1, Natalia Koudinova, Uri Nevo
1Department of Biological Regulation, The Weizmann Institute of Science, Rehovot 76100, Israel.
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.
Insights
Diffusion-weighted MRI (DW-MRI) detects early tumor response to TOOKAD-based photodynamic therapy (PDT). This method assesses photodamage and treatment success within hours, aiding prostate cancer therapy.
Area of Science:
- Oncology
- Medical Imaging
- Biochemistry
Background:
- Photodynamic therapy (PDT) utilizes photosensitizers like Pd-bacteriopheophorbide (TOOKAD) for cancer treatment.
- Early assessment of treatment efficacy is crucial for optimizing cancer therapies.
- Diffusion-weighted magnetic resonance imaging (DW-MRI) offers non-invasive insights into tissue microstructure.
Purpose of the Study:
- To evaluate DW-MRI for assessing early photodamage and treatment response following TOOKAD-based PDT.
- To investigate the biphasic changes in apparent diffusion coefficient (ADC) post-PDT.
- To correlate DW-MRI findings with histological and biochemical markers of tumor response.
Main Methods:
- Utilized human prostate adenocarcinoma xenografts (WISH-PC14) in nude mice.
- Administered TOOKAD-based photodynamic therapy (PDT).
- Performed serial DW-MRI to measure ADC changes within 24 hours post-PDT.
- Conducted in vitro studies on multicellular spheroids.
- Validated findings with histological, immunohistochemical, and serum PSA level analyses.
Main Results:
- Observed a unique biphasic change in ADC: an initial decrease followed by an increase within 24 hours post-PDT.
- DW-MRI detected successful tumor response as early as 7 hours post-treatment.
- In vitro studies indicated lipid peroxidation contributes to ADC decline.
- Significant decrease in serum PSA levels observed 7 hours post-PDT.
- Histological examinations confirmed tumor eradication.
Conclusions:
- TOOKAD-based PDT is effective in eradicating prostate adenocarcinoma xenografts.
- DW-MRI is a valuable tool for early detection of tumor response to TOOKAD-PDT.
- DW-MRI can predict treatment outcome in clinical settings for prostate cancer therapy.
