title: Activatable oligomerizable imaging agents for photoacoustic imaging of furin-like activity in living subjects.
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.
authors.affiliation: Molecular Imaging Program at Stanford and Bio-X Program, Stanford University School of Medicine, Stanford, California 94305, USA.
authors.forename: Anca
authors.initials: A
authors.lastname: Dragulescu-Andrasi
authors.forename: Sri-Rajasekhar
authors.initials: SR
authors.lastname: Kothapalli
authors.forename: Grigory A
authors.initials: GA
authors.lastname: Tikhomirov
authors.forename: Jianghong
authors.initials: J
authors.lastname: Rao
authors.forename: Sanjiv S
authors.initials: SS
authors.lastname: Gambhir
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D015195:Drug Design; D005260:Female; D045683:Furin / Q000378:metabolism*; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D051379:Mice; D057054:Molecular Imaging / Q000379:methods*; D015335:Molecular Probes / Q000737:chemistry*; D061088:Photoacoustic Techniques / Q000379:methods*; D058105:Polymerization
chemical_list: D015335:Molecular Probes; D045683:Furin