A new prostate carcinoma binding peptide (DUP-1) for tumor imaging and therapy

PURPOSE: 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...

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Main Authors: Zitzmann, Sabine (Author) , Mier, Walter (Author) , Schad, Arno (Author) , Kinscherf, Ralf (Author) , Askoxylakis, Vasileios (Author) , Krämer, Susanne (Author) , Altmann, Annette (Author) , Eisenhut, Michael (Author) , Haberkorn, Uwe (Author)
Format: Article (Journal)
Language:English
Published: January 1, 2005
In: Clinical cancer research
Year: 2005, Volume: 11, Issue: 1, Pages: 139-146
ISSN:1557-3265
Online Access:Verlag, kostenfrei, Volltext: http://clincancerres.aacrjournals.org/content/11/1/139.long
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Author Notes:Sabine Zitzmann, Walter Mier, Arno Schad, Ralf Kinscherf, Vasileios Askoxylakis, Susanne Krämer, Annette Altmann, Michael Eisenhut, Uwe Haberkorn

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245 1 2 |a A new prostate carcinoma binding peptide (DUP-1) for tumor imaging and therapy  |c Sabine Zitzmann, Walter Mier, Arno Schad, Ralf Kinscherf, Vasileios Askoxylakis, Susanne Krämer, Annette Altmann, Michael Eisenhut, Uwe Haberkorn 
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520 |a PURPOSE: 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. EXPERIMENTAL DESIGN: 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. 
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650 4 |a Dose-Response Relationship, Drug 
650 4 |a Humans 
650 4 |a Animals 
650 4 |a Microscopy, Confocal 
650 4 |a Protein Binding 
650 4 |a Male 
650 4 |a Neoplasms 
650 4 |a Neoplasm Transplantation 
650 4 |a Rats 
650 4 |a Antigens, Neoplasm 
650 4 |a Fluorescein-5-isothiocyanate 
650 4 |a Kinetics 
650 4 |a Mice 
650 4 |a Mice, Nude 
650 4 |a Microscopy, Fluorescence 
650 4 |a Peptides 
650 4 |a Prostatic Neoplasms 
650 4 |a Sensitivity and Specificity 
650 4 |a Time Factors 
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