90Y Radioactive Microsphere and its In Situ Labeling Strategy in Biological Systems for Real-Time Distribution Visualization after Embolization.

Molecular imaging is deeply involved in the 90Y selective internal radiotherapy (90Y-SIRT), exemplified as the pre-operation simulation imaging by 99mTc-MAA and postoperation imaging by 90Y bremsstrahlung SPECT or PET. However, the former was limited by the nature differences between MAA and therapeutic microspheres, and the latter was hampered by the inherent limitations of bremsstrahlung SPECT or the low positron yield of 90Y. We developed a new 90Y-microsphere and its imaging protocol. Streptavidin-decorated polystyrene microspheres (SPS) were synthesized as the embolic agent. A complementary imaging pair, 68Ga-labeled biotin ([68Ga]Ga-Biotin), was designed for in situ labeling. After intra-arterial embolization of natY-SPS, [68Ga]Ga-Biotin was administrated via vein to specifically bind to pre-localized microspheres, thus achieving in situ labeling and self-reporting of the distribution by PET imaging. The SPS exhibited excellent 90Y capture capacity in vitro, and 90Y-SPS demonstrated stability in PBS and serum. When [68Ga]Ga-Biotin was administrated separately, clear liver background was observed to provide high contrast. When [68Ga]Ga-biotin was administrated to rat pre-embolized with natY-SPS, it could rapidly recognize and bind to natY-SPS to report their in vivo distribution. Hepatic-pulmonary shunt and hepatic-abdominal shunt of SPS were calculated. When loaded peritumorally, 90Y-SPS showed strong antitumor effects while remained low biological toxicity. Tumor inhibition rate was nearly 90%. This bioorthogonal in situ labeling platform overcame the critical imaging limitations of conventional 90Y-SIRT. It provided a robust method to self-report the spatial distribution of therapeutic microspheres via PET imaging, while maintained the strong antitumor effects.