You have accessJournal of UrologyImaging/Radiology: Uroradiology1 Apr 20112317 GHRELIN RECEPTOR LABELING AS A NOVEL IMAGING MARKER FOR PROSTATIC NEOPLASMS Chen Lu, Andrew Williams, Susanne Chan, Mark McFarland, Jose Gomez-Lemus, Joseph Chin, Jonathan Izawa, Leonard Luyt, and John Lewis Chen LuChen Lu London, Canada More articles by this author , Andrew WilliamsAndrew Williams London, Canada More articles by this author , Susanne ChanSusanne Chan London, Canada More articles by this author , Mark McFarlandMark McFarland London, Canada More articles by this author , Jose Gomez-LemusJose Gomez-Lemus London, Canada More articles by this author , Joseph ChinJoseph Chin London, Canada More articles by this author , Jonathan IzawaJonathan Izawa London, Canada More articles by this author , Leonard LuytLeonard Luyt London, Canada More articles by this author , and John LewisJohn Lewis London, Canada More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2011.02.2563AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Ghrelin is a natural growth hormone secretagogue. The co-expression of ghrelin and its receptor GHS-R has been demonstrated in human prostate cancer cell lines. We wished to investigate the ghrelin receptor as a target for molecular imaging strategies in human prostate cancer. A fluorescent ghrelin analogue was synthesized and its specificity assessed in the human prostate cancer PC-3 cell line and human prostate tissue ex vivo. METHODS A ghrelin(1-18) analogue was synthesized using an APEX 396 peptide synthesizer and labeled with fluorescein via conjugation to a Lys19 at the C-terminus. Purity was determined by reverse phase HPLC and the peptide was characterized by ESI+ mass spectrometry. Ghrelin probes were incubated with PC-3 cells and a blocking study was performed in the presence of 10 times concentration of unlabeled ghrelin(1-18) analogue. The detection of ghrelin probe binding was amplified with an anti-fluorescein antibody, and relative intensities were quantified using image analysis. To assess the selectivity of the ghrelin analogue for prostate cancer over prostate intraepithelial neoplasia(PIN) or benign tissue, an ex vivo binding study was performed. Prostate core biopsy samples were collected from fresh surgery specimens of 20 patients undergoing radical prostatectomy, and serial frozen sections were made for both HE staining and ghrelin probe hybridization. Prostate tissue was categorized into prostate cancer (PCa), prostate intraepithelial neoplasia(PIN) or benign tissue based on the pathological changes in HE staining. Ghrelin staining was captured by fluorescence confocal microscopy and quantified by image analysis. RESULTS The binding of the Ghrelin probe to PC-3 cells was GHS-R dependent, as it was effectively blocked by the competitive binding of the unlabeled probe (p=0.007). Ghrelin probe signal intensity varied with different histological findings. The mean signal intensity in PIN and PCa was 2.16 and 2.42 times that of benign tissue respectively. Each pathological subgroup was statistically distinguishable from the other (PCa vs. Benign, p□f0.01; PIN vs. Benign, p=0.017; PCa vs. PIN, p=0.001). In addition, the hybridization of ghrelin probe to prostate tissue ex vivo was blocked in the presence of excess unlabeled probe. CONCLUSIONS We present here a novel ghrelin probe that, in our ex vivo analysis, was able to distinguish benign tissue from PIN and PIN from prostate cancer in patient tissues. This reveals ghrelin receptor targeting as a potentially useful strategy for molecular imaging of prostatic neoplasms in both localized and metastatic disease. © 2011 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 185Issue 4SApril 2011Page: e929 Advertisement Copyright & Permissions© 2011 by American Urological Association Education and Research, Inc.MetricsAuthor Information Chen Lu London, Canada More articles by this author Andrew Williams London, Canada More articles by this author Susanne Chan London, Canada More articles by this author Mark McFarland London, Canada More articles by this author Jose Gomez-Lemus London, Canada More articles by this author Joseph Chin London, Canada More articles by this author Jonathan Izawa London, Canada More articles by this author Leonard Luyt London, Canada More articles by this author John Lewis London, Canada More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...