Activatable Oligomerizable Imaging Agents for Photoacoustic
Imaging of Furin-Like Activity in Living Subjects
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Abstract
Photoacoustic (PA) imaging is continuing
to be applied for physiological
imaging and more recently for molecular imaging of living subjects.
Owing to its high spatial resolution in deep tissues, PA imaging holds
great potential for biomedical applications and molecular diagnostics.
There is however a lack of probes for targeted PA imaging, especially
in the area of enzyme-activatable probes. Here we introduce a molecular
probe, which upon proteolytic processing is retained at the site of
enzyme activity and provides PA contrast. The probe oligomerizes via
a condensation reaction and accumulates in cells and tumors that express
the protease. We demonstrate that this probe reports furin and furin-like
activity in cells and tumor models by generating a significantly higher
PA signal relative to furin-deficient and nontarget controls. This
probe could report enzyme activity in living subjects at depths significantly
greater than fluorescence imaging probes and has potential for molecular
imaging in deep tumors