Chemical Exchange Saturation Transfer Magnetic Resonance Imaging (CEST MRI) in Lung Cancer: A Narrative Review of Translational Challenges and Clinical Potential

Chemical exchange saturation transfer magnetic resonance imaging (CEST MRI) is a sophisticated molecular imaging technique that facilitates the indirect detection of low-concentration endogenous metabolites through their exchange with bulk water. By applying a selective radiofrequency (RF) saturation pulse to labile protons - such as those found in amide, amine, and hydroxyl groups - CEST MRI generates a measurable reduction in the water signal. This sensitivity allows for the non-invasive assessment of critical physiological variables, including pH, protein concentration, and metabolite levels. In the context of oncology, specific applications such as amide proton transfer (APT) and acidoCEST have emerged as powerful tools for probing the hallmarks of malignancy, such as tissue acidosis and altered protein expression, which are often invisible to conventional anatomical imaging. Despite the historical challenges of thoracic MRI, including respiratory motion and susceptibility artifacts at air-tissue interfaces, advancements in hardware and pulse sequences have paved the way for CEST applications in lung imaging. Lung cancer remains a leading cause of global cancer mortality, necessitating more nuanced diagnostic tools to differentiate between malignant and benign lesions and to monitor therapeutic response at a biochemical level. This narrative review explores the fundamental principles and current research regarding CEST MRI in lung malignancies. By providing a molecular-level characterization of the tumor microenvironment, CEST MRI holds the potential to serve as a functional biomarker, enhancing the precision of early diagnosis, tumor subtyping, and longitudinal management of lung cancer patients.