Development of a 111In-labeled peptide derivative targeting a chemokine receptor, CXCR4, for imaging tumors
Development of a 111In-labeled peptide derivative targeting a chemokine receptor, CXCR4, for imaging tumors
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DOI：
10.1016/j.nucmedbio.2006.01.006
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发表时间：
2006-05-01
影响因子：
3.1
通讯作者：
Saji, Hideo
中科院分区：
文献类型：
--
作者：
Hanaoka, Hirofumi;Mukai, Takahiro;Saji, Hideo
趋化因子受体CXCR 4在肿瘤细胞中高度表达，在肿瘤转移中起重要作用。本研究的目的是开发一种用于体内CXCR 4表达肿瘤成像的放射性药物。基于构效关系，我们设计了一个14个残基的肽CXCR 4抑制剂，Ac-TZ 14011，作为放射性标记肽的前体。For.在~（111）-标记中，二乙烯三胺五乙酸（DTPA）被连接到D-Lys（8）的侧链上，该侧链远离拮抗活性所必需的残基。In-DTPA-Ac-TZ 14011以浓度依赖性方式抑制天然配体--正常细胞衍生因子-1 α与CXCR 4的结合，IC 50为7.9 nM（Ac-TZ 14011：1.2 nM）。在生物分布实验中，更多的In-111-DTPA-Ac-TZ 14011积累在CXCR 4表达肿瘤中，而不是在血液或肌肉中。此外，通过共注射Ac-TZ 14011，肿瘤与血液和肿瘤与肌肉的比率显著降低，表明CXCR 4介导的肿瘤中的积累。这些发现表明（111）Wn-DTPA-Ac-TZ 14011将是用于体内转移性肿瘤中CXCR 4表达成像的潜在药剂。(c)2006年爱思唯尔公司All rights reserved.
The chemokine receptor CXCR4 is highly expressed in tumor cells and plays an important role in tumor metastasis. The aim of this study was to develop a radiopharmaceutical for the imaging of CXCR4-expressing tumors in vivo. Based on structure-activity relationships, we designed a 14-residue peptidic CXCR4 inhibitor, Ac-TZ14011, as a precursor for radiolabeled peptides. For. In-111-labeling, diethylenetriaminepentaacetic acid (DTPA) was attached to the side chain of D-Lys(8) which is distant from the residues indispensable for the antagonistic activity. In-DTPA-Ac-TZ14011 inhibited the binding of a natural ligand, strormal cell-derived factor-1 alpha, to CXCR4 in a concentration-dependent manner with an IC50 of 7.9 nM (Ac-TZ14011: 1.2 nM). In biodistribution experiments, more In-111-DTPA-Ac-TZ14011 accumulated in the CXCR4-expressing tumor than in blood or muscle. Furthermore, the tumor-to-blood and tumor-to-muscle ratios were significantly reduced by coinjection of Ac-TZ14011, indicating a CXCR4-mediated accumulation in tumor. These findings suggested that (111)Wn-DTPA-Ac-TZ14011 would be a potential agent for the imaging of CXCR4 expression in metastatic tumors in vivo. (c) 2006 Elsevier Inc. All rights reserved.