title: Ghrelin receptor as a novel imaging target for prostatic neoplasms.
abstract: BACKGROUND
  Ghrelin is a natural growth hormone secretagogue (GHS) that is co-expressed with its receptor GHSR in human prostate cancer (PCa) cells. Imaging probes that target receptors for ghrelin may delineate PCas from benign disease. The specificity of a novel ghrelin-imaging probe for PCa over normal tissue or benign disease was assessed.
  
  
  METHODS
  A fluorescein-bearing ghrelin analogue was synthesized (fluorescein-ghrelin(1-18)), and its application for imaging was evaluated in a panel of PCa cell lines and human prostate tissue. Prostate core biopsy samples were collected from fresh surgery specimens of 13 patients undergoing radical prostatectomy. Ghrelin probe signal was detected and quantified in each sample using a hapten amplification technique and associated with pathological features.
  
  
  RESULTS
  The ghrelin probe was taken up by GHSR-expressing LNCaP and PC-3 cells, and not in BPH cells that express low levels of GHSR. Binding was blocked by competition with excess unlabeled probe. The ghrelin probe signal was 4.7 times higher in PCa compared to benign hyperplasia tissue (P = 0.0027) and normal tissue (P = 0.0093). Furthermore, while the ghrelin probe signal was 1.9-fold higher in PIN compared to benign hyperplasia (P = 0.0022) and normal tissue (P = 0.0047), there was no significant difference in the signal of benign hyperplasia compared to normal tissue.
  
  
  CONCLUSIONS
  The imaging probe fluorescein-ghrelin(1-18) is specific for PCa, and did not associate significantly with benign hyperplasia or normal prostate tissue. This data suggests that ghrelin analogues may be useful as molecular imaging probes for prostatic neoplasms in both localized and metastatic disease.
authors.affiliation: Translational Prostate Cancer Research Group, London Regional Cancer Program, London, Ontario, Canada.
authors.forename: Chen
authors.initials: C
authors.lastname: Lu
authors.forename: Mark S
authors.initials: MS
authors.lastname: McFarland
authors.forename: Rae-Lynn
authors.initials: RL
authors.lastname: Nesbitt
authors.forename: Andrew K
authors.initials: AK
authors.lastname: Williams
authors.forename: Susanne
authors.initials: S
authors.lastname: Chan
authors.forename: Jose
authors.initials: J
authors.lastname: Gomez-Lemus
authors.forename: Anna Maria
authors.initials: AM
authors.lastname: Autran-Gomez
authors.forename: Ali
authors.initials: A
authors.lastname: Al-Zahrani
authors.forename: Joseph L
authors.initials: JL
authors.lastname: Chin
authors.forename: Jonathan I
authors.initials: JI
authors.lastname: Izawa
authors.forename: Leonard G
authors.initials: LG
authors.lastname: Luyt
authors.forename: John D
authors.initials: JD
authors.lastname: Lewis
mesh_terms: D000230:Adenocarcinoma / Q000175:diagnosis / Q000378:metabolism* / Q000473:pathology*; D014408:Biomarkers, Tumor / Q000378:metabolism*; D001706:Biopsy; D002460:Cell Line; D045744:Cell Line, Tumor; D003937:Diagnosis, Differential; D019793:Fluorescein; D054439:Ghrelin / Q000378:metabolism; D006801:Humans; D008297:Male; D011467:Prostate / Q000378:metabolism / Q000473:pathology; D011470:Prostatic Hyperplasia / Q000378:metabolism / Q000473:pathology; D011471:Prostatic Neoplasms / Q000175:diagnosis* / Q000378:metabolism* / Q000473:pathology; D054440:Receptors, Ghrelin / Q000378:metabolism*; D012680:Sensitivity and Specificity
chemical_list: D014408:Biomarkers, Tumor; D054439:Ghrelin; D054440:Receptors, Ghrelin; D019793:Fluorescein