PET Enabled Microspheres for Radioembolization of Liver Tumors

描述（由申请人提供）：目前的放射性栓塞Y-90微球已被普遍认为是治疗原发性和转移性肝肿瘤的最新技术。然而，由于缺乏用于剂量和治疗计划的准确诊断成像，以及在Y-90微球给药期间缺乏图像引导和剂量构象，临床结果差异很大。研究小组已经确定了将PET显像剂沿着与Y-90一起使用的可行性。所有关键特性均已按建议进行了论证。该拟议的II期研究重点是在Y-90的治疗水平下制备放射性栓塞Y-90微球，提高人员安全性，并重点关注Y-90剂量分布的校准，这对于实时Y-90剂量测定至关重要且实用，以提高非常期望的疗效。该拟议II期研究的目标是（1）建立用于按需生产Y-90微球的微制造工艺，该微球针对剂量规划和Y-90放射栓塞的患者特异性;（2）实时可靠地评估Y-90分布并实时校准Y-90剂量测定，以最大限度地降低患者安全风险并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对人类临床研究的认可;和（4）通过将Y-90剂量分布和肿瘤反应相关联，在适当的动物模型中证明临床前功效。拟议的II期研究的成功完成可能会提高患者的安全性，可能会将Y- 90放射栓塞从姑息治疗推进到肝癌的治愈性治疗。此外，这种先进的开发有可能大幅降低Y-90放射性栓塞剂的成本，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.