Title | Detection of early prostate cancer using a hepsin-targeted imaging agent. |
Publication Type | Journal Article |
Year of Publication | 2008 |
Authors | Kelly KA, Setlur SR, Ross R, Anbazhagan R, Waterman P, Rubin MA, Weissleder R |
Journal | Cancer Res |
Volume | 68 |
Issue | 7 |
Pagination | 2286-91 |
Date Published | 2008 Apr 1 |
ISSN | 1538-7445 |
Keywords | Animals, Cell Line, Tumor, Humans, Male, Mice, Mice, Nude, Peptide Library, Prostatic Neoplasms, RNA, Messenger, Serine Endopeptidases, Transfection, Tumor Markers, Biological |
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. |
DOI | 10.1158/0008-5472.CAN-07-1349 |
Alternate Journal | Cancer Res. |
PubMed ID | 18381435 |
PubMed Central ID | PMC2709884 |
Grant List | P50 CA086355 / CA / NCI NIH HHS / United States P50 CA086355-03 / CA / NCI NIH HHS / United States P50-CA090381 / CA / NCI NIH HHS / United States P50-CA86355 / CA / NCI NIH HHS / United States R01AG21404 / AG / NIA NIH HHS / United States R24 CA092782 / CA / NCI NIH HHS / United States R24 CA092782-05 / CA / NCI NIH HHS / United States R24-CA92782 / CA / NCI NIH HHS / United States U54 CA119349 / CA / NCI NIH HHS / United States U54 CA119349-040003 / CA / NCI NIH HHS / United States U54-CA119349 / CA / NCI NIH HHS / United States |