title: The gastrin/cholecystokinin-B receptor on prostate cells--a novel target for bifunctional prostate cancer imaging.
abstract: The means of identifying prostate carcinoma and its metastases are limited. The contrast agents used in magnetic resonance imaging clinical diagnostics are not taken up into the tumor cells, but only accumulate in the interstitial space of the highly vasculated tumor. We examined the gastrin/cholecystokinin-B receptor as a possible target for prostate-specific detection using the C-terminal seven amino acid sequence of the gastrin peptide hormone. The correct sequence and a scrambled control sequence were coupled to the fluorescent dye rhodamine and the magnetic resonance imaging contrast agent gadolinium (Gd)-1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA). Expression analysis of the gastrin receptor mRNA was performed by reverse transcriptase polymerase chain reaction on PC3 prostate carcinoma cells, U373 glioma, U2OS osteosarcoma and Colo205 colon carcinoma cells. After having confirmed elevated expression of gastrin receptor in PC3 cells and very low expression of the receptor in Colo205 cells, these two cell lines were used to create tumor xenografts on nude mice for in vivo experiments. Confocal lasers scanning microscopy and magnetic resonance imaging showed a high specificity of the correct conjugate for the PC3 xenografts. Staining of the PC3 xenografts was much weaker with the scrambled conjugate while the Colo205 xenografts showed no marked staining with any of the conjugates. In vitro experiments comparing the correct and scrambled conjugates on PC3 cells by magnetic resonance relaxometry and fluorescence-activated cell sorting confirmed markedly higher specificity of the correct conjugate. The investigations show that the gastrin receptor is a promising tumor cell surface target for future prostate-cancer-specific imaging applications.
authors.affiliation: Department of Neuroradiology, University of Tübingen, Germany; Peptide Synthesis Laboratory, Interfaculty Institute of Biochemistry, University of Tübingen, Germany. Electronic address: alexsturzu@yahoo.de.
authors.forename: Alexander
authors.initials: A
authors.lastname: Sturzu
authors.affiliation: Department of Neuroradiology, University of Tübingen, Germany.
authors.forename: Uwe
authors.initials: U
authors.lastname: Klose
authors.affiliation: Peptide Synthesis Laboratory, Interfaculty Institute of Biochemistry, University of Tübingen, Germany.
authors.forename: Sumbla
authors.initials: S
authors.lastname: Sheikh
authors.affiliation: Peptide Synthesis Laboratory, Interfaculty Institute of Biochemistry, University of Tübingen, Germany.
authors.forename: Hartmut
authors.initials: H
authors.lastname: Echner
authors.affiliation: Peptide Synthesis Laboratory, Interfaculty Institute of Biochemistry, University of Tübingen, Germany.
authors.forename: Hubert
authors.initials: H
authors.lastname: Kalbacher
authors.affiliation: Mass Spectrometry Laboratory, Medicinal Research Centre, University of Tübingen, Germany.
authors.forename: Martin
authors.initials: M
authors.lastname: Deeg
authors.affiliation: Department of Neuroradiology, University of Tübingen, Germany.
authors.forename: Thomas
authors.initials: T
authors.lastname: Nägele
authors.affiliation: Department of Urology, University of Tübingen, Germany.
authors.forename: Christian
authors.initials: C
authors.lastname: Schwentner
authors.affiliation: Department of Neuroradiology, University of Tübingen, Germany.
authors.forename: Ulrike
authors.initials: U
authors.lastname: Ernemann
authors.affiliation: Department of Neuroradiology, University of Tübingen, Germany.
authors.forename: Stefan
authors.initials: S
authors.lastname: Heckl
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D003287:Contrast Media; D005456:Fluorescent Dyes / Q000737:chemistry; D005682:Gadolinium; D005755:Gastrins / Q000737:chemistry; D006573:Heterocyclic Compounds, 1-Ring; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D051379:Mice; D008819:Mice, Nude; D009842:Oligopeptides / Q000737:chemistry; D011467:Prostate / Q000166:cytology; D011471:Prostatic Neoplasms / Q000175:diagnosis / Q000235:genetics*; D043887:Receptor, Cholecystokinin B / Q000235:genetics*; D012235:Rhodamines / Q000737:chemistry
chemical_list: D003287:Contrast Media; D005456:Fluorescent Dyes; D005755:Gastrins; D006573:Heterocyclic Compounds, 1-Ring; D009842:Oligopeptides; D043887:Receptor, Cholecystokinin B; D012235:Rhodamines; C071349:1,4,7,10-tetraazacyclododecane- 1,4,7,10-tetraacetic acid; D005682:Gadolinium; C029773:rhodamine B
keywords: Bimodal contrast agent; Gastrin receptor; Magnetic resonance imaging; Prostate cancer