MRI Probes for In Vivo Aldehyde Sensing

Endogenous aldehydes are produced via tightly regulated metabolic processes and are rapidly cleared by aldehyde dehydrogenases. However, dysregulation of these processes leads to accumulation of toxic aldehydes in affected tissues, resulting in electrophilic stress forming pathogenic DNA- and protein-adducts. The highly reactive aldehydes contribute to numerous pathologies including traumatic brain injury, cancer, cardiovascular diseases, and fibrosis. Due to their transient nature and electrophilicity, the development of molecular imaging probes with the ability to trap and detect aldehydes in vivo remains a challenge. Herein, two classes of aldehyde-mapping MRI probes are discussed: (1) gadolinium and manganese-containing macrocyclic MRI agents targeting extracellular aldehydes produced during active tissue fibrosis, and (2) metal-free hydrazoCEST-MRI agents for total intracellular aldehyde detection. This comprehensive review outlines the development, mechanisms, and potential applications of diverse MRI probes targeting aldehydes, aiming to advance non-invasive diagnostic tools, disease staging, and therapeutic interventions in multiple pathologies.