title: Treatment Effects of WST11 Vascular Targeted Photodynamic Therapy for Urothelial Cell Carcinoma in Swine.
abstract: Surgical management of upper tract urothelial carcinoma requires kidney and ureter removal, compromising renal function. Nonsurgical alternatives have potentially prohibitive safety concerns. We examined the feasibility and safety of ablation of the ureter and renal pelvis using endoluminal vascular targeted photodynamic therapy in a porcine model. We also report the efficacy of WST11 vascular targeted photodynamic therapy in a murine model.
  
  
  
  After receiving approval we performed a total of 28 endoluminal ablations in the ureters and renal pelvis of 18 swine. Intravenous infusion of WST11 (4 mg/kg) followed by 10-minute laser illumination was done via percutaneous access or a retrograde ureteroscopic approach. Animals were followed clinically with laboratory testing, imaging and histology, which were evaluated at several postablation time points. A murine xenograft was created with the 5637 human urothelial cell carcinoma line to determine sensitivity to this therapy.
  
  
  
  At 24 hours 50 mW/cm laser fluence produced superficial necrosis of the ureter. Deeper necrosis penetrating the muscularis propria or adventitia was produced by treatment with 200 mW/cm in the ureter and the renal pelvis. At 4 weeks superficial urothelium had regenerated over the treatment site. No symptomatic obstruction, clinically relevant hydronephrosis or abnormality of laboratory testing was noted up to 4 weeks. Of the mice 80% had no evidence of tumor 19 days after WST11 vascular targeted photodynamic therapy.
  
  
  
  Urothelial cell carcinoma appears to be sensitive to WST11 vascular targeted photodynamic therapy. The depth of WST11 vascular targeted photodynamic therapy treatment effects can be modulated in a dose dependent manner by titrating light intensity. Moreover, when applied to the porcine upper urinary tract, this treatment modality is feasible via antegrade and retrograde access.
authors: Urology Service, Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, New York.
authors: Katie S
authors: KS
authors: Murray
authors: Center of Comparative Medicine and Pathology, Memorial Sloan Kettering Cancer Center, New York, New York; Department of Urology, New York Presbyterian Hospital, New York, New York; Weill-Cornell Medical College, New York Presbyterian Hospital, New York, New York; New York Presbyterian Hospital, New York, New York; Rockefeller University, New York, New York.
authors: Ashley G
authors: AG
authors: Winter
authors: Sloan Kettering Institute, Memorial Sloan Kettering Cancer Center, New York, New York.
authors: Renato Beluco
authors: RB
authors: Corradi
authors: Sloan Kettering Institute, Memorial Sloan Kettering Cancer Center, New York, New York.
authors: Stephen
authors: S
authors: LaRosa
authors: Sloan Kettering Institute, Memorial Sloan Kettering Cancer Center, New York, New York.
authors: Sylvia
authors: S
authors: Jebiwott
authors: Sloan Kettering Institute, Memorial Sloan Kettering Cancer Center, New York, New York.
authors: Alexander
authors: A
authors: Somma
authors: Interventional Radiology Service, Department of Radiology, Memorial Sloan Kettering Cancer Center, New York, New York.
authors: Haruyuki
authors: H
authors: Takaki
authors: Interventional Radiology Service, Department of Radiology, Memorial Sloan Kettering Cancer Center, New York, New York.
authors: Govindarajan
authors: G
authors: Srimathveeravalli
authors: Laboratory of Comparative Pathology, Memorial Sloan Kettering Cancer Center, New York, New York.
authors: Michelle
authors: M
authors: Lepherd
authors: Laboratory of Comparative Pathology, Memorial Sloan Kettering Cancer Center, New York, New York.
authors: Sebastien
authors: S
authors: Monette
authors: Sloan Kettering Institute, Memorial Sloan Kettering Cancer Center, New York, New York.
authors: Kwanghee
authors: K
authors: Kim
authors: Department of Plant and Environmental Sciences, Weizmann Institute of Science, Rehovot, Israel.
authors: Avigdor
authors: A
authors: Scherz
authors: Urology Service, Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, New York; Department of Urology, New York Presbyterian Hospital, New York, New York. Electronic address: colemanj@mskcc.org.
authors: Jonathan A
authors: JA
authors: Coleman
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D001429:Bacteriochlorophylls / Q000627:therapeutic use*; D002295:Carcinoma, Transitional Cell / Q000188:drug therapy*; D045744:Cell Line, Tumor; D005260:Female; D006801:Humans; D008297:Male; D051379:Mice; D008819:Mice, Nude; D010778:Photochemotherapy / Q000379:methods*; D017319:Photosensitizing Agents / Q000627:therapeutic use*; D011897:Random Allocation; D013552:Swine; D016896:Treatment Outcome; D001749:Urinary Bladder Neoplasms / Q000188:drug therapy*; D023041:Xenograft Model Antitumor Assays
chemical_list: D000970:Antineoplastic Agents; D001429:Bacteriochlorophylls; D017319:Photosensitizing Agents; C503696:padeliporfin
keywords: WST11 compound; kidney neoplasms; photochemotherapy; ureteral neoplasms; urothelium