NE-AUA 2006 Annual Meeting, September 28 - 30, 2006, The Westin Hotel & Rhode Island Convention Center Providence, Rhode Island
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Increases in Tumor Vascular Permeability after Treatment With PDT in Prostate Cancer
Curtis Crane, MD, Bin Chen.
Dartmouth Hitchcock, Lebanon, NH,

Background: Photodynamic therapy (PDT) has been shown to be a promising minimally invasive treatment for prostate cancer by targeting prostate cancer cells. Targeting and damaging tumor vasculature with the goal of increasing vascular permeability and therefore potentially enhance chemotherapeutic delivery to PDT treated tumors has not been studied before. We analyzed PDT's effect on prostate cancer vasculature with the hypothesis that increases in permeability in the tumor vasculature can be achieved using this modality.
Methods: Athymic mice inoculated with a green fluorescence protein, MAT-Ly-Lu (GFP-MLL) prostate cancer cell line in the thigh were treated with vascular targeting PDT for 500 seconds and compared to controls infected with the same cancer cell line. The photosensitizer verteporfin (0.25 mg/kg) was injected 15 minutes before treatment with a 690 nanometer laser light at 50 mW/cm2. Tetramethylrhodamine-labeled albumin was injected immediately after PDT treatment and the extravasation of tetramethylrhodamine-labeled albumin was imaged with 535/40 nm excitation and 590 nm long pass emission filters. Fluorescence images were captured with a SensiCam QE high performance digital CCD camera (The Cook Corp, Auburn Hills, MI) and analyzed using NIH ImageJ software. To determine the microscopic distribution of tetramethylrhodamine-labeled albumin, animals were euthanized at different time points after injection. Using a fluorescence microscope, extravasation was noted in frozen tumor sections
Results: Compared to controls, tumors treated with vascular targeting PDT showed a rapid increase in flourescence intensity from 500 to 770mfi in the first four hours where the intensity peaked. After six hours, flourescence intensity returned to a baseline of 500mfi where the control value was maintained for the duration of the experiment. The average mean flourescence intensity for treated mice was 570mfi, 720 mfi, 770mfi and 420mfi at one hour, three hours, six hours and 20 hours, respectively. The average mean flourescence intensity for controls was 500mfi, 550mfi and 420mfi at one and three hours, six hours and 20 hours, respectively.
Conclusions: In this case control study, PDT targeting tumor vasculature was shown to cause increased permeability of dye macroscopically. Ultimately, the clinical relevance would lie in enhancing anticancer drug delivery to tumors that have had damaged vasculature by PDT. Further study is warranted to determine if this increase in permeability may be utilized to enhance drug delivery to tumors.


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