Hyperactivation of monoamine oxidase enzymes (MAO) is associated with uncontrolled production of neurotoxic compounds such as reactive oxygen species, whose accumulation is linked to neurodegenerative, chronic, and age-related diseases. Although chromo-fluorogenic probes for detecting and quantifying MAO activity have been reported, non-invasive methods for monitoring MAO overexpression in vivo remain elusive. Here, we report a renal-clearable fluorogenic probe based on the cyanine-7 fluorophore (Cy7-MAO) for in vivo detection of MAO overexpression through a simple measurement of the fluorescence in urine. The probe incorporates sulfonic acid moieties for renal clearance and a propylamino group as a MAO substrate. Upon administration, Cy7-MAO is hydrolysed at the site by MAO, releasing a highly emissive Cy7 fluorophore, which is excreted in urine and quantified by fluorescence. Cy7-MAO is validated in vitro using HepG2 liver human cells, which express elevated MAO levels. We further demonstrate the in vivo applicability of Cy7-MAO for MAO activity monitoring in aged mice, which show significantly higher urine fluorescence than young mice, consistent with an elevated MAO activity in older animals. These findings support Cy7-MAO as a tool for longitudinal assessment of MAO activity in vivo, providing a novel approach to study MAO-related pathologies.
Domínguez et al. (Mon,) studied this question.