Synthesis and in vivo evaluation of radiohalogen-labeled antitumor cyclic peptides

Yamada, Keiichi*; Watanabe, Shigeki; Ohshima, Yasuhiro; Hanaoka, Hirofumi*; Tsukui, Narutaka*; Takano, Chikako*; Yamaguchi, Aiko*; Oku, Hiroyuki*; Ishioka, Noriko

Sansalvamide A (SA) is a marin-derived cyclic depsipeptide that exhibits cytotoxicity against colon cancer cell line. Recently, a series of cyclic pentapeptide analogs of SA in which Hmp ((2S)-2-hydroxy-4-methylpentanoic acid) residue was replaced by amino acids or N-methyl-amino acids were synthesized. We previously reported that the haogenated analog of [MeLeu]SA, namely SA-Br, SA-I, SA-Cl, exhibited potent cytotoxicity against MDA-MB-231. In the present study, we considered to evaluate in vivo biodistribution, stability and antitumor activity of these halogenated SA peptides in tumor-bearing mice. For this purpose, radiohalogen atoms are most suitable for labeling without changing their primary structure and biological activity. Here, we report the synthesis and in vivo biodistribution of I-labeled SA analog (SA-[I]).