期刊
JOURNAL OF MEDICINAL CHEMISTRY
卷 50, 期 18, 页码 4295-4303出版社
AMER CHEMICAL SOC
DOI: 10.1021/jm060887v
关键词
-
资金
- NCRR NIH HHS [RR03037-08, G12 RR003037] Funding Source: Medline
- NIGMS NIH HHS [S06 GM060654-050009, S06 GM60654, S06 GM060654, S06 GM060654-080009, S06 GM060654-070009, S06 GM060654-060009] Funding Source: Medline
The early and later eluting [(TcO)-Tc-99m]depreotide products on RP-HPLC were confirmed to be the anti and syn diastereomers, respectively, based on proton NMR and circular dichroism spectroscopy. NMR provided evidence of a folded, conformationally constrained structure for the syn diastereomer. The syn diastereomer is predominant (anti/syn similar to 10:90) in the [(TcO)-Tc-99m]depreotide preparation and shows a slightly higher affinity (IC50 = 0.15 nM) for the somatostatin receptor than the anti diastereomer (IC50 = 0.89 nM). Both diastereomers showed higher binding affinities than the free peptide (IC50 = 7.4 nM). Biodistribution studies in AR42J tumor xenograft nude mice also showed higher tumor uptake for syn [(TcO)-Tc-99m]depreotide (6.58% ID/g) than for the anti [(TcO)-Tc-99m]depreotide (3.38% ID/g). Despite the differences in biological efficacy, the favorable binding affinity, tumor uptake, and tumor-to-background ratio results for both diastereometic species predict that both are effective for imaging somatostatin receptor-positive tumors in vivo.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据