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.