title: Detection of early prostate cancer using a hepsin-targeted imaging agent.
abstract: Early detection and diagnosis of prostate cancer is key to designing effective treatment strategies. Microarrays have resulted in the discovery of hepsin (HPN) as a biomarker for detection of prostate cancer. In this study, we explore the development of HPN imaging probes for detection of prostate cancer. We used phage display to isolate HPN binding peptides with 190 + 2.2 nmol/L affinity in monomeric form and high specificity. The identified peptides were able to detect human prostate cancer on tissue microarrays and in cell-based assays. HPN-targeted imaging agents were synthesized by conjugating multiple peptides to fluorescent nanoparticles to further improve avidity through multivalency and to improve pharmacokinetics. When injected into mouse xenograft models, HPN-targeted nanoparticles bound specifically to HPN-expressing LNCaP xenografts compared with non-HPN-expressing PC3 xenografts. HPN imaging may provide a new method for detection of prostate cancer.
authors.affiliation: Center for Molecular Imaging Research, Massachusetts General Hospital and Harvard Medical School, Charlestown, MA 02129, USA. kkelly9@partners.org
authors.forename: Kimberly A
authors.initials: KA
authors.lastname: Kelly
authors.forename: Sunita R
authors.initials: SR
authors.lastname: Setlur
authors.forename: Robert
authors.initials: R
authors.lastname: Ross
authors.forename: Rajesh
authors.initials: R
authors.lastname: Anbazhagan
authors.forename: Peter
authors.initials: P
authors.lastname: Waterman
authors.forename: Mark A
authors.initials: MA
authors.lastname: Rubin
authors.forename: Ralph
authors.initials: R
authors.lastname: Weissleder
mesh_terms: D000818:Animals; D014408:Biomarkers, Tumor / Q000032:analysis* / Q000096:biosynthesis / Q000235:genetics; D045744:Cell Line, Tumor; D006801:Humans; D008297:Male; D051379:Mice; D008819:Mice, Nude; D019151:Peptide Library; D011471:Prostatic Neoplasms / Q000175:diagnosis* / Q000201:enzymology* / Q000235:genetics; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D012697:Serine Endopeptidases / Q000032:analysis* / Q000096:biosynthesis / Q000235:genetics; D014162:Transfection
chemical_list: D014408:Biomarkers, Tumor; D019151:Peptide Library; D012333:RNA, Messenger; D012697:Serine Endopeptidases; C055645:hepsin