Detection of early prostate cancer using a hepsin-targeted imaging agent.
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.
Kelly
Kimberly A
KA
Center for Molecular Imaging Research, Massachusetts General Hospital and Harvard Medical School, Charlestown, MA 02129, USA. kkelly9@partners.org
Setlur
Sunita R
SR
Ross
Robert
R
Anbazhagan
Rajesh
R
Waterman
Peter
P
Rubin
Mark A
MA
Weissleder
Ralph
R
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
D014408:Biomarkers, Tumor; D019151:Peptide Library; D012333:RNA, Messenger; D012697:Serine Endopeptidases; C055645:hepsin