title: Endoscopic vascular targeted photodynamic therapy with the photosensitizer WST11 for benign prostatic hyperplasia in the preclinical dog model.
abstract: OBJECTIVE
  Vascular targeted photodynamic therapy with WST11 (TOOKAD® 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.
  
  
  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 periurethral necrosis with endothelial layer destruction and adjacent inflammation/atrophy 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.
authors.affiliation: Urologic Oncology Research Group, McGill University Health Centre-Research Institute, Montreal, Quebec, Canada. Electronic address: simone.chevalier@mcgill.ca.
authors.forename: Simone
authors.initials: S
authors.lastname: Chevalier
authors.forename: Fabio L
authors.initials: FL
authors.lastname: Cury
authors.forename: Eleonora
authors.initials: E
authors.lastname: Scarlata
authors.forename: Ehab
authors.initials: E
authors.lastname: El-Zayat
authors.forename: Lucie
authors.initials: L
authors.lastname: Hamel
authors.forename: Joice
authors.initials: J
authors.lastname: Rocha
authors.forename: Fatima Z
authors.initials: FZ
authors.lastname: Zouanat
authors.forename: Sabri
authors.initials: S
authors.lastname: Moussa
authors.forename: Avigdor
authors.initials: A
authors.lastname: Scherz
authors.forename: Mostafa
authors.initials: M
authors.lastname: Elhilali
authors.forename: Maurice
authors.initials: M
authors.lastname: Anidjar
mesh_terms: D000818:Animals; D001429:Bacteriochlorophylls / Q000627:therapeutic use*; D004195:Disease Models, Animal; D004285:Dogs; D004353:Drug Evaluation, Preclinical; D004724:Endoscopy; D008297:Male; D010778:Photochemotherapy / Q000379:methods*; D017319:Photosensitizing Agents / Q000627:therapeutic use*; D011467:Prostate / Q000098:blood supply; D011470:Prostatic Hyperplasia / Q000628:therapy*
chemical_list: D001429:Bacteriochlorophylls; D017319:Photosensitizing Agents; C503696:padeliporfin
keywords: BPH; CP; LUTS; UPP; US; VTP; WST11 compound; benign prostatic hyperplasia; closure pressure; dogs; lower urinary tract symptoms; photodynamic therapy; prostate; prostatic hyperplasia; ultrasound; urethral pressure profile; vascular targeted photodynamic