PURPOSE - Surgical management of upper tract urothelial carcinoma requires removal of kidney and ureter, compromising renal function. Non-surgical alternatives have potentially prohibitive safety concerns. We examine the feasibility and safety of ablation of the ureter and renal pelvis using endoluminal vascular-targeted photodynamic therapy in a porcine model and report efficacy of WST11 vascular-targeted photodynamic therapy in a murine model.
MATERIALS AND METHODS - Following approval, we performed 28 endoluminal ablations in the ureters and renal pelvis of 18 swine. Intravenous infusion of WST11 (4mg/kg) followed by laser illumination (10 minutes) was performed via percutaneous access or retrograde ureteroscopic approach. Animals were followed clinically with laboratory testing, imaging and histology was evaluated at several post-ablation time points. A murine xenograft was created with the 5637 human urothelial cell carcinoma line to determine sensitivity to this therapy.
RESULTS - At 24 hours, 50 mW/cm laser fluence produced superficial necrosis of the ureter and deeper necrosis (penetrating the muscularis propria or adventitia) was produced by treatment with 200 mW/cm in the ureter and renal pelvis. At 4 weeks, superficial urothelium had regenerated over the treatment site. No symptomatic obstruction, clinically relevant hydronephrosis, or abnormality of lab testing was noted up to 4 weeks. In mice, 80% had no evidence of tumor at 19 days after WST11 vascular-targeted photodynamic therapy.
CONCLUSIONS - Urothelial cell carcinoma appears to be sensitive to WST11 vascular-targeted photodynamic therapy. Depth of WST11 vascular-targeted photodynamic therapy treatment effects can be modulated in a dose-dependent manner by titration of light intensity. Moreover, this treatment modality, applied to the porcine upper urinary tract, is feasible via antegrade and retrograde access.
The Journal of urology. 2016 Feb 06 [Epub ahead of print]
Katie S Murray, Ashley G Winter, Renato Beluco Corradi, Stephen LaRosa, Sylvia Jebiwott, Alexander Somma, Haruyuki Takaki, Govindarajan Srimathveeravalli, Michelle Lepherd, Sebastien Monette, Kwanghee Kim, Avigdor Scherz, Jonathan A Coleman
Urology Service, Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY. , Department of Urology, New York Presbyterian Hospital, Weill-Cornell Medical College, New York, NY. , Sloan Kettering Institute, Memorial Sloan Kettering Cancer Center, New York, NY. , Sloan Kettering Institute, Memorial Sloan Kettering Cancer Center, New York, NY. , Sloan Kettering Institute, Memorial Sloan Kettering Cancer Center, New York, NY. , Sloan Kettering Institute, Memorial Sloan Kettering Cancer Center, New York, NY. , Interventional Radiology Service, Department of Radiology, Memorial Sloan Kettering Cancer Center, New York, NY. , Interventional Radiology Service, Department of Radiology, Memorial Sloan Kettering Cancer Center, New York, NY. , Laboratory of Comparative Pathology, Center of Comparative Medicine & Pathology, Memorial Sloan Kettering Cancer Center, Weill-Cornell Medical College, and The Rockefeller University, New York, NY. , Laboratory of Comparative Pathology, Center of Comparative Medicine & Pathology, Memorial Sloan Kettering Cancer Center, Weill-Cornell Medical College, and The Rockefeller University, New York, NY. , Sloan Kettering Institute, Memorial Sloan Kettering Cancer Center, New York, NY. , Department of Plant and Environmental Sciences, Weizmann Institute of Science, Rehovot, Israel. , Urology Service, Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY; Department of Urology, Weill-Cornell Medical College.