Hypoxia Imaging as a Radiomics Signature in Tumors Using Novel ¹⁹ F-Eu-Based Contrast Agents for Magnetic Resonance Imaging

The ability to accurately identify and characterize regions of hypoxia has been an active area of study due to the biological ramifications of low oxygen tension in different pathological conditions, including inflammation, infections, wound healing, cardiovascular conditions, kidney and pulmonary diseases, hepatic and neurological toxicities, and cancer. Although hypoxia contributes a significant role in these conditions, the ability to accurately and instantaneously monitor the presence of hypoxia in vivo and correlate comprehensive analysis of hypoxia-dependent molecular signatures in response to treatments regimens is lacking. With the advent of hypoxia-responsive contrast agents for magnetic resonance imaging (MRI), including the recent development and characterization by our team of a novel probe that involves both ¹⁹ F and Eu ^II , the capability to integrate direct hypoxia imaging in real-time with new technologies that enable spatial transcriptomic profiling has become a possibility. To assess the capability of this agent for studying hypoxia, we used osteosarcoma as a model. In this preliminary study we demonstrate two major results: First, we show that convection-enhanced delivery (CED) is a reliable and robust methodology to distribute MRI contrast agents throughout a tumor. Second, we show that integration of direct hypoxia-detecting imaging modalities and spatial biology enables real-time in vivo insights into biology and identification of biomarkers directly applicable to disease development and response to therapy. The ability to identify and define hypoxia-mediated biology using direct rather than indirect MRI methods has extremely significant implications in the care of a wide-range of pathological conditions. Consequently, the framework outlined in these preliminary studies is applicable to other pathological conditions and provides the basis for direct in vivo hypoxia detection, monitoring, and biological analyses with translational applications to patient care and management.