Image-based treatment planning for TLD1433 mediated intraoperative photodynamic therapy with an optical surface applicator-A translational rodent study.

Abstract

Several clinical studies suggest that following surgical resection, intraoperative photodynamic therapy (intraoperative PDT) has the potential to reduce local recurrence and improve overall survival in patients diagnosed with pleural dissemination of lung cancer. The response to intraoperative PDT depends on the light dose rate (irradiance) and dose (fluence) as well as the intratumoral concentration of the photosensitizer and oxygenation. We seek to advance intraoperative PDT by improving the control of irradiance and fluence with image-based treatment planning for an optical surface applicator (OSA) with a novel photosensitizer (TLD1433) that has shown safety in recent clinical trials. To that end, we tested the accuracy of Monte Carlo-based simulations of light delivery from the OSA in vitro and in vivo. We assess the safety and biodistribution after the instillation of TLD1433 in the peritoneal cavity of mice and rats, and define the relationship between the intratumoral irradiance and fluence, and the volume of tumor ablation in the peritoneal cavity of rats. The Monte Carlo simulations agreed with light dosimetry measurements at a 5-mm prescription depth in vitro. An instillation of TLD1433 in the peritoneal cavity of mice is safe and leads to drug accumulation in the tumor and adjacent organs in the peritoneal cavity of rats. A TLD1433-mediated intraoperative PDT procedure using an instilled dose of 14 mg/kg and 532-nm laser light induces tumor cell degradation in the peritoneal cavity of rats. Our results suggest that the Monte Carlo simulation can be used as an image-based treatment plan for administering a controlled PDT procedure with OSA and TLD1433.