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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

View larger version (21K): [in a new window]   FIGURE 1. Amino acid sequence of bacterial clones enriched through selection rounds and identified by sequencing. The part of the thioredoxin loop sequence CPG...GPC forming the loop via disulfide bridge is shown.

View larger version (19K): [in a new window]   FIGURE 2. In vitro binding assay with MM-2Y. 125I-MM-2Y was added to wells with PC-3, HUVEC, or PNT-2 cells and incubated for 1 h. Experiments were performed in triplicate; mean value of 5 independent experiments (n = 3 for PNT-2 cells) and SE are shown. – = no competitor was added; + = 10–4 mol of unlabeled MM-2 per liter was added as competitor 30 min before incubation with labeled MM-2.

View larger version (9K): [in a new window]   FIGURE 3. Serum stability of MM-2. MM-2 peptide was incubated with human serum. After the indicated incubation times, samples were analyzed with HPLC to show possible degradation of peptide.

View larger version (16K): [in a new window]   FIGURE 4. Biodistribution of MM-2Y in male BALB/c nu/nu mice carrying PC-3 tumors (n = 3 animals per time point). Animals were injected intravenously with 131I-MM-2Y, and percentage injected dose per gram of tissue (%ID/g) was measured in tumor and control organs after 15 min, 45 min, 135 min, and 24 h.