Abstract 3468: Endoscopic diagnosis and treatment of esophageal tumor using a novel DDS-type photoactivatable agent

Abstract

Abstract Introduction: Photodynamic diagnosis (PDD) and therapy (PDT) have been clinically used for the early phase cancer of hollow organs. We are advancing the photomedicine to the next stage, in which treatment is carried out immediately after the detection of lesions. For achieving the simultaneous diagnosis and treatment, we established a novel DDS-type photoactivatable agent, micelle-based photosensitizer loading dendrimer porphyrin (DP/M). A micelle-based shell structure is expected to be selectively accumulated in tumors. An intensely emitted fluorescence from porphyrin can be used for lesion detection and a highly quantum yield of porphyrin promises an effective PDT. Apart from the agent, we recently developed a fluorometric system equipped with an ultrathin endoscope that has a spatial resolution of 15,000 pixels even with a diameter of 0.8 mm. The aim of this study was to verify practical effectiveness of the novel photosensitizer combined with the endoscopic fluorometric system for simultaneous diagnosis and treatment. In this study, we targeted esophageal cancer because satisfactory results are not always obtained with conventional therapies and an endoscopic approach is applicable. Materials and Methods: A rat orthotopic esophageal tumor model was established in female Fischer F344 rats by orally administered with NMBuA (N-Nitroso Methylbutylamine) solved in drinking water. After intravenous administration of DP/M, PDD was carried out using the endoscopic fluorometric system (ex. 405 nm, em. > 630 nm). After the detection of lesions, tumors were irradiated using a diffuser tip fiber connected to a 635nm LD laser. Results: About 6 weeks after the administration of NMBuA, polypoid tumors were observed in the esophagus. Pathological analysis revealed that proliferated polymorphonuclear cells were seen: a part of which reached the muscular layer of mucosa. A selective accumulation of DP/M in the tumors was confirmed with the endoscopic fluorometric system. This modality enabled repeated observations of tumors without sacrifice. The following PDT provided a promising result. Conclusions: DP/M combined with the endoscopic fluorometric system brought the simultaneous diagnosis and treatment for the orthotopic rat esophagus tumor models. Acknowledgment: This research is granted by the Japan Society for the Promotion of Science (JSPS) through the “Funding Program for World-Leading Innovative R&D on Science and Technology (FIRST Program),” initiated by the Council for Science and Technology Policy (CSTP). Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 3468. doi:1538-7445.AM2012-3468