MP61-06 PHOTODYNAMIC THERAPY FOR NON-MUSCLE INVASIVE BLADDER CANCER MEDIATED BY INSTILLED PHOTOSENSITIZER TLD1433 AND GREEN LIGHT ACTIVATION

You have accessJournal of UrologyBladder Cancer: Basic Research & Pathophysiology II1 Apr 2016MP61-06 PHOTODYNAMIC THERAPY FOR NON-MUSCLE INVASIVE BLADDER CANCER MEDIATED BY INSTILLED PHOTOSENSITIZER TLD1433 AND GREEN LIGHT ACTIVATION Savo Lazic, Pavel Kaspler, Arkady Mandel, Michael A.S. Jewett, Girish Kulkarni, and Lothar Lilge Savo LazicSavo Lazic , Pavel KasplerPavel Kaspler , Arkady MandelArkady Mandel , Michael A.S. JewettMichael A.S. Jewett , Girish KulkarniGirish Kulkarni , and Lothar LilgeLothar Lilge View All Author Informationhttps://doi.org/10.1016/j.juro.2016.02.880AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Bladder cancer is the most common malignant tumor in the urinary tract and accounts for 3.3% of all cancers. An estimated 72,570 new bladder cancer cases occurred in the US in 2013 and resulted in approximately 15,210 deaths. Transurethral resection of a bladder tumor is the standard first line treatment. Although effective at treating the tumor, the recurrence rate ranges from 60% to 70%. Photodynamic therapy (PDT), where a photosensitizer (PS) converts light into cytotoxic radical oxygen species to cause cell death, was initially approved for bladder cancer in 1993. It failed in clinical trials due to morbidity affecting the muscle layers, resulting in reduced bladder volume and incontinence. Here we present a new approach to PDT treatment of bladder cancer using the novel ruthenium based PS (TLD1433), 525 nm activation wavelength, both allowing for steep dose gradients. The AY-27 rat orthotopic cancer model was used to test PDT efficacy. METHODS Rat bladders were sensitized to tumor cell seeding by an acid/base wash. 1,500,000 AY-27 cells were infused into the bladder for one hour. Tumors grew to treatment size within 2 to 3 weeks. TLD1433 was infused into the bladder for one hour at 0.6 (N=18) or 6.0 (N=9) mg/ml. Immediately afterwards, the bladder was washed and irradiated with 525 nm laser light to a target radiant exposure of 90 J/cm^2. Bladder tissue and tumors were collected two days later and histologically analyzed with H&E staining. RESULTS TLD1433-only or light-only treatment showed no effect on tumor growth, healthy urothelium, or bladder musculature. After PDT treatment with TLD1433, full depth tumor necrosis was observed at both 0.6 and 6.0 mg/mL concentrations in the vast majority of tumors. Incidence of muscle invasive tumors were also destroyed by the PDT treatment. Healthy bladder muscle tissue was unaffected after PDT treatment. Urothelium showed local inflammation near the tumor that was beginning to heal at the time of fixation. CONCLUSIONS TLD1433 is a new ruthenium based photosensitizer that is able to cause full depth tumor destruction after only one hour bladder incubation. A clinical trial testing the ability of TLD1433 mediated PDT to prevent recurrence after transurethral resection of a bladder tumor is planned using instillation of the drug and intraoperative irradiance quantification with a novel dosimetry cage. © 2016FiguresReferencesRelatedDetails Volume 195 Issue 4S April 2016 Page: e805 Advertisement Copyright & Permissions© 2016Metrics Author Information Savo Lazic More articles by this author Pavel Kaspler More articles by this author Arkady Mandel More articles by this author Michael A.S. Jewett More articles by this author Girish Kulkarni More articles by this author Lothar Lilge More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...