PET Enabled Microspheres for Radioembolization of Liver Tumors

描述(申请人提供)：目前放射栓塞剂Y-90微球已被公认为治疗原发和转移性肝脏肿瘤的最先进技术。然而，由于缺乏对剂量和治疗计划的准确诊断成像，以及在Y-90微球给药过程中缺乏图像指导和剂量构象，临床结果差异很大。调查小组已经确定了将PET显像剂与Y-90一起使用的可行性。所有关键的可行性都已按照提议进行了论证。这项拟议的第二阶段研究集中在Y-90治疗水平的放射性栓塞剂Y-90微球的制备上，以增强人员安全性，并集中于Y-90剂量分布的校准，这对于实时Y-90剂量测量是关键和实用的，以提高非常期望的疗效。这项拟议的第二阶段研究的目标是(1)建立按需生产Y-90微球的微制造工艺，这些微球用于剂量规划和Y-90放射栓塞术；(2)可靠地实时评估Y-90分布，并实时校准Y-90剂量学，以最大限度地降低患者的安全风险和最大限度地提高治疗效果；(3)建立可接受的临床前生物相容性和放射毒性，以获得FDA接受用于人类临床研究；(4)通过将Y-90剂量分布与肿瘤反应相关联，在合适的动物模型中展示临床前的疗效。拟议的第二阶段研究的成功完成可能会改善患者的安全性，可能会将Y-90放射栓塞术从姑息治疗推进到肝癌的根治性治疗。此外，这一先进的发展有可能大幅降低Y-90放射栓塞剂的成本，从而使这种治疗方案更容易负担得起。

DESCRIPTION (provided by applicant): 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 along with Y-90. All key feasibilities have been demonstrated as proposed. This proposed Phase II research focuses on the preparation of radioembolic Y-90 microspheres at therapeutic levels of Y-90 with enhanced personnel safety and focuses on the calibration of Y-90 dose distribution that are critical and practical for real-time Y-90 dosimetry o improve much desired efficacy. The objectives of this proposed Phase II research is (1) to establish micro-fabrication process for on-demand production of Y-90 microspheres that are patient specific for dose planning and Y-90 radioembolization; (2) to reliably assess Y-90 distribution in real-time and to calibrate Y-90 dosimetry also in real-time to minimize patient safety risk and to maximize treatment efficacy; (3) to establish acceptable preclinical biocompatibility and radio-toxicity in order to gain FDA acceptance for human clinical investigation; and (4) to demonstrate preclinical efficacy in an appropriate animal model through correlating Y-90 dose distributions and tumor responses. Successful completion of the proposed Phase II research will likely improve patient safety, will likely advance Y- 90 radioembolization from palliative treatment to curative treatment for liver cancer. In addition, this advanced development has the potential to drastically reduce the cost of Y-90 radioembolization agents such that this treatment option is more affordable.