Synthesis and biological evaluation of EC20:: A new folate-derived, 99mTc-based radiopharmaceutical
Synthesis and biological evaluation of EC20:: A new folate-derived, 99mTc-based radiopharmaceutical
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DOI：
10.1021/bc0200430
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发表时间：
2002-11-01
影响因子：
4.7
通讯作者：
Douglas, N
中科院分区：
文献类型：
--
作者：
Leamon, CP;Parker, MA;Douglas, N
设计了一种新的叶酸肽衍生物来有效协调 Tc-99m。这种新的螯合物（称为 EC20）被发现能够以时间和浓度依赖性方式与培养的叶酸受体 (FR) 阳性肿瘤细胞结合，并且具有非常高的亲和力（K-D 类似于 3 nM）。使用体外相对亲和力测定，还发现当单独存在或作为配制的金属螯合物存在时，EC20 可以有效地与 H-3-叶酸竞争细胞结合。静脉注射入Balb/c小鼠后，Tc-99m-EC20迅速从循环中去除（血浆t(1/2)类似于4分钟）并以非代谢形式排泄到尿液中。在 M109 荷瘤 Balb/c 小鼠中进行的伽玛闪烁扫描和定量生物分布研究的数据证实，99mTc-EC20 主要积聚在 FR 阳性肿瘤和肾组织中。这些结果表明，Tc-99m-EC20 在临床上可用作非侵入性放射诊断成像剂，用于检测 FR 阳性人类癌症。
A new peptide derivative of folic acid was designed to efficiently coordinate Tc-99m. This new chelate, referred to as EC20, was found to bind cultured folate receptor (FR)-positive tumor cells in both a time- and concentration-dependent manner with very high affinity (K-D similar to 3 nM). Using an in vitro relative affinity assay, EC20 was also found to effectively compete with H-3-folic acid for cell binding when presented either alone or as a formulated metal chelate. Following intravenous injection into Balb/c mice, Tc-99m-EC20 was rapidly removed from circulation (plasma t(1/2) similar to 4 min) and excreted into the urine in a nonmetabolized form. Data from gamma scintigraphic and quantitative biodistribution studies performed in M109 tumor-bearing Balb/c mice confirmed that 99mTc-EC20 predominantly accumulates in FR-positive tumor and kidney tissues. These results suggest that Tc-99m-EC20 may be clinically useful as a noninvasive radiodiagnostic imaging agent for the detection of FR-positive human cancers.