Ratiometric MRI probes for tumor microenvironment profiling: Design principles, multimodal validation, and future perspectives in precision oncology

Abstract

Magnetic resonance imaging (MRI) is a non-invasive, radiation-free diagnostic tool widely used for anatomical and functional imaging in tumor diagnosis. However, its clinical utility is limited by inherent sensitivity constraints. While MRI probes can be designed to target and respond to specific biomolecules, offering valuable insights into the tumor microenvironment (TME). Despite these advancements, traditional MRI probes often fall short in providing quantitative assessments of the TME, limiting their ability to support precise tumor diagnosis and staging. In recent years, ratiometric MRI probes have emerged as a promising solution, combining targeted imaging with quantitative analysis capabilities. This review provides a comprehensive overview of the latest developments in ratiometric MRI probes, detailing their design principles, key components, and experimental validation methods. We begin by elucidating the fundamental mechanisms of ratiometric MRI techniques, including diaCEST, paraCEST, MRET, and dual-modality imaging. Subsequently, we highlight recent research efforts focused on the development of ratiometric MRI probes for the quantitative detection of tumor-associated molecules, such as enzymes, reactive oxygen species (ROS), glutathione (GSH), and dual-response stimuli. Finally, we discuss the current challenges in the field and propose future directions to advance the application of ratiometric MRI probes in tumor diagnosis and therapy. This review aims to provide a critical resource for researchers and clinicians, offering insights into how ratiometric MRI probes can overcome existing limitations and pave the way for more precise and personalized tumor diagnostics.