PET Enabled Microspheres for Radioembolization of Liver Tumors

描述（由申请人提供）：目前放射栓塞Y-90微球已被普遍认为是治疗原发性和转移性肝脏肿瘤的最新技术。然而，由于在给药Y-90微球期间缺乏准确的剂量和治疗计划诊断成像，以及缺乏图像引导和剂量配置，临床结果差异很大。调查小组已经确定了与Y-90一起使用PET显像剂的可行性。所有关键的可行性都已按照建议进行了论证。本II期研究的重点是制备具有放射栓塞作用的Y-90微球，达到治疗水平，提高人员安全性，并重点校正Y-90剂量分布，这是实时Y-90剂量测定的关键和实用，以提高期望的疗效。这项拟议的II期研究的目标是：(1)建立按需生产Y-90微球的微制造工艺，该微球可用于剂量规划和Y-90放射栓塞；(2)实时可靠地评估Y-90分布并实时校准Y-90剂量，以最大限度地降低患者安全风险并最大化治疗效果；(3)建立可接受的临床前生物相容性和放射毒性，以便获得FDA对人体临床研究的认可；(4)通过Y-90剂量分布与肿瘤反应的相关性，在适当的动物模型中证明临床前疗效。成功完成拟议的II期研究可能会提高患者的安全性，可能会将Y- 90放射栓塞从姑息性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，使这种治疗选择更实惠。

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.