Abstract
Hypoxia is a major driver of tumor progression and therapeutic resistance, with hypoxia-inducible factor 2α (HIF-2α) playing a critical regulatory role. To address the current lack of noninvasive imaging tools for HIF-2α, we developed [(18)F]-TC-S 7009, the F-18 labeled PET tracer designed to target HIF-2α. The probe was synthesized via copper-mediated fluorination, achieving high radiochemical purity and strong binding affinity for HIF-2α (K (d) = 81 nM). In vivo PET/CT imaging in U87 glioblastoma-bearing mice demonstrated efficient blood-brain barrier penetration, modest tumor uptake, and favorable tumor-to-background contrast. Blocking experiments confirmed receptor-specific binding. Region-specific brain accumulation was observed in the hippocampus, striatum, and hypothalamus. These findings establish [(18)F]-TC-S 7009 as a promising noninvasive molecular imaging tool for visualizing HIF-2α activity, providing a foundation for future investigations into hypoxia-driven tumor biology and the development of targeted therapies.