Synthesis and Biodistribution of a Cyclic Peptide Containing NGR Motif as a Potential Tumor Angiogenesis Imaging Agent

Abstract

Abstract: In order to evaluate the potency of short peptides containing NGR motif as the imaging agents for diagnosis of tumor angiogenesis, a preliminary investigation on the synthesis and biodistrubution of a short peptide containing the NGR motif was carried out and the results are reported in the present paper. The open-chain peptide GGCNGRC was first cyclized to GG(CNGRC) by oxygen oxidation, and then coupled with benzoyl-protected N-hydroxysuccinimidyl-MAG₃ to form Bz-MAG₃-GG(CNGRC). The latter was labeled with ^{^99m}Tc by reduction-ligand substitution procedure, while the benzoyl group was removed simultaneously. The labeled complex ^{^99m}Tc-MAG₃-GG(CNGRC) was isolated by HPLC and purified by reverse-phase sep-pak column. Its radiochemical purity was estimated to be better than 90%. The complex was stable in saline and serum. The biodistribution of ^{^99m}Tc-MAG₃-GG(CNGRC) in normal and tumor-bearing mice indicates that it is quickly distributed to the whole body and excreted via both hepatobiliary tract and kidney-urethra systems. ^{^99m}Tc-MAG₃-GG(CNGRC) was accumulated in zenografted colon carcinoma (CL-187) after 3 h post injection. It is expected that the radiolabeled short peptides containing NGR motif may be useful as diagnostic imaging agents for tumor angiogenesis.

Key words: NGR, Tumor, Angiogenesis, MAG₃, CD13

CLC Number:

O615

TrendMD:

ZHANG Tao, WANG Yi, CHU Tai-Wei, LIU Xin-Qi, HU Shao-Wen, WANG Xiang-Yun . Synthesis and Biodistribution of a Cyclic Peptide Containing NGR Motif as a Potential Tumor Angiogenesis Imaging Agent[J]. Chem. J. Chinese Universities, 2005, 26(5): 801.

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