AbstractBACKGROUNDGhrelin 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.METHODSA 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.RESULTSThe 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.CONCLUSIONThe 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. Prostate 72:825–833, 2012. © 2011 Wiley Periodicals, Inc.