Endoscopic Vascular Targeted Photodynamic Therapy with the Photosensitizer WST11 for Benign Prostatic Hyperplasia in the Preclinical Dog Model Simone Chevalier,* Fabio L. Cury, Eleonora Scarlata, Ehab El-Zayat, Lucie Hamel, Joice Rocha, Fatima Z. Zouanat, Sabri Moussa, Avigdor Scherz, Mostafa Elhilali† and Maurice Anidjar From the Urologic Oncology Research Group, McGill University Health Centre-Research Institute (SC, ES, EEZ, LH, JR, FZZ, SM, ME, MA), Division of Radiation Oncology, Department of Oncology, McGill University Health Center (FLC) and Department of Urology, Jewish General Hospital (MA), Montreal, Quebec, Canada, and Weizmann Institute of Science (AS), Rehovot, Israel Purpose: Vascular targeted photodynamic therapy with WST11 (TOOKADÒ Soluble) is in phase III clinical trials of an interstitial transperineal approach for focal therapy of prostate cancer. We investigated the safety and efficacy of the endourethral route in the context of benign prostatic hyperplasia in the dog model. Materials and Methods: An optical laser fiber was positioned in the prostatic urethra of 34 dogs, including 4 controls. It was connected to a 753 nm diode laser at 200 mW/cm fluence, delivering 200 to 300 J. WST11 (5 to 15 mg/kg) was infused intravenously in 2 modes, including continuous, starting 5 to 15 minutes before and during illumination, or a bolus 5 to 10 minutes before illumination. Prostate ultrasound, cystourethrogram, urodynamics and histopathology were performed. Followup was 1 week to 1 year. Results: Endourethral WST11 vascular targeted photodynamic therapy was uneventful in all except 1 dog, which experienced urinary retention but reached the 1-week end point. All prostates except those in controls showed hemorrhagic lesions. They consisted of 2 levels of concentric alterations, including periure- thral necrosis with endothelial layer destruction and adjacent inflammation/at- rophy with normal blood vessels. Prostatic urethral width increased as early as 6 weeks after treatment, while prostatic volume decreased, reaching 25% by 18 to 26 weeks. A parallel decrease in urethral pressure at 6 weeks lasted up to 1 year. Conclusions: We confirmed the vascular effect of endourethral WST11 vascular targeted photodynamic therapy. To our knowledge we report for the first time that the resulting periurethral necrosis led to significant, sustained widening of the prostatic urethra, accompanied by long-term improvement in urodynamic parameters. These findings support future clinical applications of this minimally invasive approach to benign prostatic hyperplasia. Key Words: prostate, prostatic hyperplasia, photodynamic therapy, WST11 compound, dogs BENIGN prostatic hyperplasia is a his- tological disease that develops in 50% of men older than 40 years and is increasing in incidence in older men, including in up to 70% by age 70 years in North America. 1 Of these men 30% Abbreviations and Acronyms BPH ¼ benign prostatic hyperplasia CP ¼ closure pressure LUTS ¼ lower urinary tract symptoms UPP ¼ urethral pressure profile US ¼ ultrasound VTP ¼ vascular targeted photodynamic Accepted for publication May 7, 2013. Study received approval from the animal ethics committees of McGill University, Montreal and McGill University Health Centre-Research Institute. Supported by STEBA Biotech, Paris, France. * Correspondence: Division of Urology, McGill University Health Centre-Research Institute, R1-137, 1650 Cedar Ave., Montreal, Quebec, Canada, H3G 1A4 (e-mail: simone.chevalier@ mcgill.ca ). † Financial interest and/or other relationship with Sophiris Pharma, Eli Lilly, Triton Pharm Canada, Astellas Canada, Ferring Canada, Pfizer Canada, Lumenis and AMS. 1946 j www.jurology.com 0022-5347/13/1905-1946/0 THE JOURNAL OF UROLOGY ® © 2013 by AMERICAN UROLOGICAL ASSOCIATION EDUCATION AND RESEARCH,INC. http://dx.doi.org/10.1016/j.juro.2013.05.014 Vol. 190, 1946-1953, November 2013 Printed in U.S.A.