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Detection of Early Prostate Cancer Using a Hepsin-Targeted Imaging Agent

¹ Center for Molecular Imaging Research, Massachusetts General Hospital and Harvard Medical School; ² Center for Systems Biology, Massachusetts General Hospital and Department of Systems Biology, Harvard Medical School; ³ Department of Pathology, Brigham and Women's Hospital and Harvard Medical School; ⁴ The Dana-Farber Harvard Cancer Center, Boston, Massachusetts; ⁵ MIT Center for Cancer Research; and ⁶ The Broad Institute of Massachusetts Institute of Technology and Harvard, Cambridge, Massachusetts

Requests for reprints: Kimberly Kelly, Center for Molecular Imaging Research, Massachusetts General Hospital, Harvard Medical School, 149 13th Street, Room 5420 Charlestown, MA 02129. Phone: 617-726-5784; E-mail: kkelly9{at}partners.org.

Key Words: prostate cancer • early detection • molecular imaging

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. [Cancer Res 2008;68(7):2286–91]

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