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Evaluation of a new TAG-72 binding peptide

¹ Radiology, University of Massachusetts Medical School, Worcester, Massachusetts

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Objectives: This laboratory has used phage display to identify novel peptides with binding affinity for TAG-72. We have now synthesized the most promising peptide, GGVSCMQTSPVCENNL (A2-6), and evaluated its properties in vitro and in vivo in tumored mice.

Methods: The peptide was both radiolabeled with 99mTc and biotinylated. The radiolabeled peptide was used to confirm serum stability and to estabish its distribution and clearance in tumor-bearing mice while the biotinylated peptide was used for histology. Both were used to confirm TAG-72 binding specificity.

Results: RP and SE HPLC demonstrated stability of the 99mTc labeled peptide in 37oC human serum through 2 h. By flow cytometry, binding of the biotinylated peptide to TAG-72 positive LS174T cells was shown to be concentration dependent as expected for specific binding and with only background binding to control TAG-72 negative HT-29 cells. Specificity of binding was also demonstrated with the 99mTc labeled peptide that showed inhibited binding to LS174T cells with increasing concentrations of unlabeled peptide. Immnuohistochemical staining of LS-174T tumor xenograph sections for the biotinylated A2-6 peptide was similar to that for the TAG-72 positive B72.3 antibody. The 99mTc-A2-6 biodistribution in LS-174T tumored mice showed rapidly decreasing blood levels with evidence of hepatobilliary clearance and with a tumor to normal leg ratio reaching a maximum of 2.6 at 30 min. Tumor accumulation was reduced 6-fold with pre administration of excess unlabeled peptide.

Conclusions: When isolated from its phage, the A2-6 peptide shows favorable specificity of binding and tumor accumulation to be considered further as a potential imaging agent for TAG-72 positive cancers.

This Article Services Email this article to a friend Similar articles in this journal Alert me to new issues of the journal Download to citation manager Google Scholar Articles by Chen, L. Articles by Rusckowski, M. PubMed Articles by Chen, L. Articles by Rusckowski, M.