title: A new prostate carcinoma binding peptide (DUP-1) for tumor imaging and therapy.
abstract: OBJECTIVE
  Prostate carcinomas belong to the most widespread tumors, and their number is increasing. Imaging modalities used for diagnosis, such as ultrasound, computed tomography, and positron emission tomography, often produce poor results. Radiolabeled peptides with high sensitivity and specificity for prostate cancer would be a desirable tool for tumor diagnosis and treatment.
  
  
  METHODS
  We used phage display and the prostate-specific membrane antigen-negative cell line DU-145 to identify a peptide. The isolated DUP-1 was tested in vitro for its binding specificity, kinetics, and affinity. Internalization of the peptide was evaluated with confocal microscopy. The tumor accumulation in a nude mouse model was analyzed with 131I-labeled DUP-1 in PC-3 and DU-145 prostate tumors as well as in the rat prostate tumor model AT-1.
  
  
  RESULTS
  The synthesized peptide showed rapid binding kinetics peaking at 10 minutes. It shows specific binding to prostate carcinoma cells but low binding affinity to nontumor cells. Peptide binding is competed with unlabeled DUP-1, and a time-dependent internalization into DU-145 cells was shown. Biodistribution studies of DUP-1 in nude mice with s.c. transplanted DU-145 and PC-3 tumors showed a tumor accumulation of 5% and 7% injected dose per gram, and bound peptide could not be removed by perfusion. The rat prostate tumor model showed an increase of radioactivity in the prostate tumor up to 300% in comparison with normal prostate tissue.
  
  
  CONCLUSIONS
  DUP-1 holds promise as a lead peptide structure applicable in the development of new diagnostic tracers or anticancer agents that specifically target prostate carcinoma.
authors.affiliation: Clinical Cooperation Unit Nuclear Medicine, German Cancer Research Center, University of Heidelberg, Heidelberg, Germany. s.zitzmann@dkfz.de
authors.forename: Sabine
authors.initials: S
authors.lastname: Zitzmann
authors.forename: Walter
authors.initials: W
authors.lastname: Mier
authors.forename: Arno
authors.initials: A
authors.lastname: Schad
authors.forename: Ralf
authors.initials: R
authors.lastname: Kinscherf
authors.forename: Vasileios
authors.initials: V
authors.lastname: Askoxylakis
authors.forename: Susanne
authors.initials: S
authors.lastname: Krämer
authors.forename: Annette
authors.initials: A
authors.lastname: Altmann
authors.forename: Michael
authors.initials: M
authors.lastname: Eisenhut
authors.forename: Uwe
authors.initials: U
authors.lastname: Haberkorn
mesh_terms: D000818:Animals; D000951:Antigens, Neoplasm / Q000737:chemistry / Q000276:immunology*; D045744:Cell Line, Tumor; D004305:Dose-Response Relationship, Drug; D016650:Fluorescein-5-isothiocyanate / Q000737:chemistry; D006801:Humans; D007700:Kinetics; D008297:Male; D051379:Mice; D008819:Mice, Nude; D018613:Microscopy, Confocal; D008856:Microscopy, Fluorescence; D009368:Neoplasm Transplantation; D009369:Neoplasms / Q000473:pathology* / Q000628:therapy*; D010455:Peptides / Q000737:chemistry*; D011471:Prostatic Neoplasms / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D011485:Protein Binding; D051381:Rats; D012680:Sensitivity and Specificity; D013997:Time Factors; D014018:Tissue Distribution
chemical_list: D000951:Antigens, Neoplasm; C501462:DUP-1 peptide; D010455:Peptides; D016650:Fluorescein-5-isothiocyanate