Radiolabeling and biodistribution of a nasopharyngeal carcinoma-targeting peptide identified by in vivo phage display.

A dodecapeptide EDIKPKTSLAFR ligand targeting CEN-1 human nasopharyngeal carcinoma (NPC) was identified by in vivo phage display. Two tridecapeptides and their derivatives, named YR13 (YEDIKPKTSLAFR), EY13 (EDIKPKTSLAFRY), EY13-NH2 (EDIKPKTSLAFRY-NH2) and Fmoc-YR13 (Fmoc-YEDIKPKTSLAFR), were synthesized and radiolabeled with 131I. The stability in vitro, biodistribution and tissue distribution of selected phage particles in mice bearing NPC tumor were determined, and plasma metabolites analysis of radiolabeled peptides was carried out. Although Fmoc and NH2 groups could protect the peptide from deiodination, only Fmoc group inhibited the binding of Fmoc-YR13 to NPC tumors. The compound EY13-NH2, the C-terminal amide of peptide EY13, had the greatest serum stability, the least deiodination, and showed favorable tumor/blood ratios. The selected phage particles (phage 3 or phage 5) were more concentrated in NPC tumors than the control phage (initial phage display peptide library). EY13 could also inhibit the binding of selected phage particles to tumors. The results indicated that EDIKPKTSLAFR was a good candidate in diagnostic and therapeutic NPC.