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

ABSTRACT Molecular imaging is deeply involved in the 90 Y selective internal radiotherapy ( 90 Y‐SIRT), exemplified as the pre‐operation simulation imaging by 99m Tc‐MAA and postoperation imaging by 90 Y 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 90 Y. We developed a new 90 Y‐microsphere and its imaging protocol. Streptavidin‐decorated polystyrene microspheres (SPS) were synthesized as the embolic agent. A complementary imaging pair, 68 Ga‐labeled biotin ([ 68 Ga]Ga‐Biotin), was designed for in situ labeling. After intra‐arterial embolization of nat Y‐SPS, [ 68 Ga]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 90 Y capture capacity in vitro, and 90 Y‐SPS demonstrated stability in PBS and serum. When [ 68 Ga]Ga‐Biotin was administrated separately, clear liver background was observed to provide high contrast. When [ 68 Ga]Ga‐biotin was administrated to rat pre‐embolized with nat Y‐SPS, it could rapidly recognize and bind to nat Y‐SPS to report their in vivo distribution. Hepatic‐pulmonary shunt and hepatic‐abdominal shunt of SPS were calculated. When loaded peritumorally, 90 Y‐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 90 Y‐SIRT. It provided a robust method to self‐report the spatial distribution of therapeutic microspheres via PET imaging, while maintained the strong antitumor effects.