title: Radioactive smart probe for potential corrected matrix metalloproteinase imaging.
abstract: Although various activatable optical probes have been developed to visualize metalloproteinase (MMP) activities in vivo, precise quantification of the enzyme activity is limited due to the inherent scattering and attenuation (limited depth penetration) properties of optical imaging. In this investigation, a novel activatable peptide probe (64)Cu-BBQ650-PLGVR-K(Cy5.5)-E-K(DOTA)-OH was constructed to detect tumor MMP activity in vivo. This agent is optically quenched in its native form, but releases strong fluorescence upon cleavage by selected enzymes. MMP specificity was confirmed both in vitro and in vivo by fluorescent imaging studies. The use of a single modality to image biomarkers/processes may lead to erroneous interpretation of imaging data. The introduction of a quantitative imaging modality, such as PET, would make it feasible to correct the enzyme activity determined from optical imaging. In this proof of principle report, we demonstrated the feasibility of correcting the activatable optical imaging data through the PET signal. This approach provides an attractive new strategy for accurate imaging of MMP activity, which may also be applied for other protease imaging.
authors.affiliation: Molecular Imaging Center, Department of Radiology, University of Southern California, Los Angeles, CA 90033, USA.
authors.forename: Chiun-Wei
authors.initials: CW
authors.lastname: Huang
authors.forename: Zibo
authors.initials: Z
authors.lastname: Li
authors.forename: Peter S
authors.initials: PS
authors.lastname: Conti
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D005260:Female; D006801:Humans; D020782:Matrix Metalloproteinases / Q000737:chemistry / Q000378:metabolism*; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D057054:Molecular Imaging / Q000379:methods*; D015335:Molecular Probes / Q000737:chemistry; D015394:Molecular Structure; D009374:Neoplasms, Experimental / Q000175:diagnosis* / Q000201:enzymology / Q000378:metabolism; D010455:Peptides / Q000737:chemistry; D049268:Positron-Emission Tomography; D019275:Radiopharmaceuticals / Q000737:chemistry
chemical_list: D015335:Molecular Probes; D010455:Peptides; D019275:Radiopharmaceuticals; D020782:Matrix Metalloproteinases