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

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.