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.
The successful real-time quantitative dosimetry assessment has the potential to dramatically improve the efficacy of Y-90 radioembolization for the treatment of primary and metastatic tumors. It is now technologically feasible to have optimal patient dose planning and intraoperative dose escalation to the tumors without the risk of over dosing the healthy tissue or organs. Unexpected shunting of Y-90 radioembolic agents and, more importantly, over-embolization with reflux of the Y-90 agents into gastrointestinal arteries can be detected early, and corrective actions can be taken intraoperatively during the administration of the Y-90 radioembolic agents. This proposed innovative embolic agent also has the potential to become ideal dose planning surrogates to current Y-90 radioembolic microspheres (Therasphere(R) or SIR-Spheres(R)) such that much broader applicability of this development can be achieved for the maximum benefits to liver cancer patients.