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 best practice to date is to use Tc99m labeled macroaggregated albumin (Tc99m-MAA) to simulate the distribution of radioembolic Y-90 microspheres for screening patients and for dose planning and to use Bremsstrahlung radiation of Y-90 or to use the extremely low internal pair production of Y-90 to qualitatively assess the administered Y-90 only in a post-treatment procedure. The investigators propose, as the enabling step toward improving efficacy, to make microspheres PET imageable for the best sensitivity and real-time distribution of Y-90 microspheres. Microspheres with just PET isotopes (i.e. no Y-90) are ideal and invaluable for patient screening and dose and treatment planning for all Y-90 microspheres, including current Therasphere(R) and SIR-Spheres(R). Microspheres encapsulated with both PET isotopes and Y- 90 will enable intraoperative dose escalation to the tumors to enhance both safety and efficacy, and postoperative monitoring and dose confirmation. The Phase I research focuses on the preparation of microspheres with PET isotopes that accurately reveal their distribution using PET imaging techniques and other complimentary imaging techniques. The specific aims are to (1) identify compatible host matrices and compatible processing techniques for the creation of PET enabled microspheres for dose planning and for the creation of PET enabled Y-90 microspheres for radioembolization of liver tumors; (2) immobilize sufficient levels of positron emitters for optimal PET images; (3) control the cumulative radioactivity leakage from the microspheres to < 1% to ensure that PET images accurately represent the spatial distribution of Y-90 microspheres; and (4) assess preliminary biocompatibility using standard toxicity screening. The Phase II research will begin with in vivo PET imaging characterization and in vivo biocompatibility assessment and end with preliminary clinical assessment of using PET enabled microspheres for patient screening, dose planning, and intraoperative dose escalation of Y-90 microspheres to the tumors. PUBLIC HEALTH RELEVANCE: The successful introduction of positron emitting microspheres (PET microspheres) has the potential to dramatically improve the efficacy of radioembolic Y-90 microspheres for the treatment of primary and metastatic tumors in the liver by optimal patient dose planning and intraoperative dose escalation to the tumors through quantitative and real-time PET imaging. The use of PET microspheres is expected to improve the safety of Y-90 microspheres treatment of liver cancer patients through better prediction of Y-90 microspheres and real-time monitoring of the administration of Y-90 microspheres. Unexpected shunting of Y-90 microspheres and especially over-embolization with reflux of agent into gastrointestinal arteries can be detected early, and corrective actions can be taken intraoperatively during the administration of Y-90 microspheres. This project is to establish the feasibility of encapsulating (not labeling) PET isotopes and/or Y-90 isotopes in timed-bioabsorbable microspheres without radioisotope leakage. The PET enabled microspheres without Y-90 are ideal surrogates to current radioembolic microspheres (Therasphere(R) or SIR-Spheres(R)) for optimal dose and treatment planning and perfect surrogates to the next generation Y-90 microspheres, which will include companion PET radioisotopes for quantitative imaging.