Synthesis of Potential New Contrast Agents for Applications Across Multiple Imaging Modalities

Abstract

The imaging field comprises a wide array of techniques, driving the creation and innovation of contrast agents and probes. The increasing prevalence of diseases and the detection of new conditions have driven the development and adjustment of contrast agents to aid in detection, treatment and the improvement of patient outcomes. Magnetic resonance imaging (MRI) is a non-invasive imaging technique known for producing high-resolution images. To enhance resolution and improve image visualization, contrast agents can be employed to assist in the detection and diagnosis of diseases such as tumors or cancers. This thesis explores the development and application of multiple imaging modalities through the creation of diverse probes designed for specific diagnostic and therapeutic applications. The research focuses on the design, synthesis and characterization of various imaging probes, each optimized for techniques such as MRI, chemical exchange saturation transfer (CEST)-MRI, magnetic resonance fingerprinting (MRF) and optical imaging. We have identified and characterized a hydrazone-CEST MRI probe capable of mapping vitamin B6 metabolism, with applications in lung cancer models. Additionally, we have developed a novel method for combining two lanthanides within the same complex to test their potential as gadolinium-based contrast agents in MRI and MRF imaging, as well as in optical imaging, using the emissive properties of europium(III). Building on this chemistry, the plan was to incorporate the radioisotope lutetium-177 into our complex for potential future application as a targeted radionuclide therapy agent against glioblastoma. Furthermore, we attempted to develop a THC-based probe for both Δ⁸ and Δ⁹ isomers to assess their ability to track biodistribution within the endocannabinoid system and their receptors engagement. This research contributes to the advancement of medical imaging technologies by demonstrating the adaptability and effectiveness of multiple imaging modalities and the designed probes for each application.