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. The production and clearance of reactive endogenous aldehydes is tightly regulated; however, the accumulation of aldehydes contributes to numerous pathologies including brain injury, cancer, cardiovascular diseases, and fibrosis. This review explores the challenges in detecting aldehydes in vivo and outlines two classes of MRI probes targeting intracellular and extracellular aldehydes and encourages the advancement of diagnostic tools for aldehyde-related pathologies. Like the elusive meerkat rarely seen in the wild, the probe technologies reviewed herein are bringing an elusive biomarker of disease, aldehydic load, out into the open. image