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Dr. Lilge will deliver an oral and poster presentation on “TLD-1433-Mediated Photo Dynamic Therapy as a Novel Intravesical Treatment for Bladder Cancer: in vitro, in vivo, and Good Laboratory Practice (“GLP”) Toxicology Validation”. Urinary bladder cancer, which accounts for 3.3% of all cancers, is a socially significant healthcare problem that has become a major cause of morbidity, mortality, and health-related costs. Although first line treatments are initially effective at treating the tumour, the recurrence rate ranges from 60% to 70%. Photo Dynamic Therapy (“PDT”) is a medical therapy where a photosensitizer (“PS”) produces cytotoxic radical oxygen species upon light activation at a particular wavelength, causing cell death through apoptosis. PDT was initially approved by Health Canada for bladder cancer in 1993; however, the treatment has drawn criticism due to morbidity affecting the muscle layers and bladder function. Here we present a new approach to PDT treatment of bladder cancer using instillation of a novel water soluble ruthenium-based PS, known as TLD-1433 and the TLC-3200 (Theralase Inc., Toronto, Canada) laser and dosimetry system that was designed to emit and detect 525 nm laser light in the bladder. Moorfields Eye Hospital London Laser Eye Surgeon – YouTubeConfocal microscope cellular uptake studies of TLD-1433 demonstrate that TLD-1433 is primarily localized in the cellular cytoplasm. Inductively Coupled Plasma – Mass Spectrometry (“ICP-MS”) studies of tissue uptake after systemic injection in mice showed clearance within 24 hours from most tissue, while one hour TLD-1433 intravesical instillation into the rat bladder demonstrated minimal seepage into systemic circulation. Tumour versus normal urothelium uptake of TLD-1433 was measured in the orthotopic rat bladder model and preferential tumour uptake was observed (186x preferential uptake in bladder tumour versus normal urothelium). Confirmatory preclinical studies utilizing “TLD-1433 only” or “Laser light only” treatments demonstrated no discernible effects on tumor growth rate, normal urothelium or bladder musculature.
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