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Identification of a New Prostate-Specific Cyclic Peptide with the Bacterial FliTrx System

¹ Clinical Cooperation Unit Nuclear Medicine, German Cancer Research Center, Heidelberg, Germany
² Department of Nuclear Medicine, University of Heidelberg, Heidelberg, Germany
³ Department of Radiopharmaceutical Chemistry, German Cancer Research Center, Heidelberg, Germany

Peptides are useful tools for directing radioisotopes into tumors. We evaluated the ability of a bacterial peptide display system to isolate new prostate tumor-specific peptides. Methods: We used the bacterial FliTrx system to identify a new cyclic peptide that binds to prostate carcinoma. Serum stability and binding affinities of the ¹²⁵I-labeled peptide were tested. Furthermore, the ¹³¹I-labeled peptide was used to evaluate its biodistribution. Results: Several peptides showing a potential consensus motif were identified. The new peptide MM-2 is stable in serum for up to 24 h. It binds to PC-3 cells, and this binding can be inhibited more than 70% with the unlabeled peptide. Binding to human umbilical vein endothelial cells (HUVECs) and PNT-2 cells is weaker, and competition (27%) in HUVECs is less efficient. The biodistribution showed moderate accumulation in tumor. Conclusion: Bacterial peptide display, an alternative to phage peptide display, can allow the identification of specific binding and stable peptides.

Key Words: tumor targeting • prostate carcinoma • FliTrx bacterial peptide display

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