PET Enabled Y-90 Microspheres for Radioembolization of Liver Tumors

项目摘要/摘要 目前的放射性栓塞剂Y-90微球已被公认为最先进的治疗方法 原发和转移性肝脏肿瘤。然而，由于缺乏准确的临床结果，临床结果差异很大。 剂量和治疗计划的诊断成像以及缺乏图像指导和剂量构象 在Y-90微球给药过程中。调查组已经确定了 单独或与Y-90一起使用PET显像剂。所有关键的可行性都已被证明为 建议在第一阶段和第二阶段。这项拟议的第二阶段研究集中在制备放射性栓塞剂Y- Y-90治疗水平的90微球，增强了人员安全性，研究还集中在 Y-90剂量分布的刻度是Y-90实时剂量测量的关键和实用 提高非常想要的疗效。这项拟议的IIB阶段研究的目标是：(1)建立 使用商业上可行的按需生产PET发射微球的微制造工艺 玻璃组合物，(2)可靠地生产低成本的Y-90放射性同位素，(3)评估生物兼容性和 生物风险，以获得FDA对人类临床研究的认可，以及(4)证明临床 聚对苯二甲酸乙二酯发光玻璃微球的用途。成功完成拟议的第IIB阶段研究将 导致启用PET的Y-90玻璃微球，以提高患者的安全性并推进Y-90 肝癌特别是原发性肝癌的放射栓塞术从姑息性治疗到根治性治疗 癌症。此外，这一IIB阶段的高级开发有可能大幅降低 Y-90放射栓塞剂，使这种治疗方案不仅更经济实惠，而且 有效。

Project Summary/Abstract Current radioembolic Y-90 microspheres have been generally recognized as the state-of-the-art for treating primary and metastatic liver tumors. However, the clinical results vary vastly due to the lack of accurate diagnostic imaging for dose and treatment planning and the lack of image guidance and dose conformation during the administration of Y-90 microspheres. The investigation team has established the feasibility of using PET imaging agent alone or along with Y-90. All key feasibilities have been demonstrated as proposed in Phases I & II. This proposed Phase IIB research focuses on the preparation of radioembolic Y- 90 microspheres at therapeutic levels of Y-90 with enhanced personnel safety, and the research also focuses on the calibration of Y-90 dose distribution that is critical and practical for real-time Y-90 dosimetry to improve much desired efficacy. The objectives of this proposed Phase IIB research are (1) to establish a microfabrication process for on-demand production of PET emitting microspheres using commercially viable glass compositions, (2) to reliably produce low-cost Y-90 radioisotope, (3) to assess biocompatibility and biological risks to gain FDA acceptance for a human clinical investigation, and (4) to demonstrate clinical utility of PET emitting glass microspheres. Successful completion of the proposed Phase IIB research will lead to PET-enabled Y-90 glass microspheres to improve patient safety and to advance Y-90 radioembolization from palliative treatment to curative treatment for liver cancer, especially primary liver cancer. In addition, this Phase IIB advanced development has the potential to drastically reduce the cost of Y-90 radioembolization agents so that this treatment option is more affordable in addition to being more effective.