68Ga-labeled NOTA-RGD-BBN peptide for dual integrin and GRPR-targeted tumor imaging
68Ga-labeled NOTA-RGD-BBN peptide for dual integrin and GRPR-targeted tumor imaging
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DOI：
10.1007/s00259-009-1123-z
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发表时间：
2009-09-01
影响因子：
9.1
通讯作者：
Chen, Xiaoyuan
中科院分区：
文献类型：
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作者：
Liu, Zhaofei;Niu, Gang;Chen, Xiaoyuan
放射性标记的Arg-Gly-Asp（RGD）和蛙皮素（BBN）肽类似物已被广泛研究，分别用于肿瘤整合素α（v）β（3）和胃泌素释放肽受体（GRPR）表达的成像。最近，我们设计并合成了一个RGD-BBN异源二聚体肽，它是由c（RGDyK）和BBN（7-14）通过谷氨酸接头合成的。本研究的目的是研究发生器洗脱的Ga-68标记的RGD-BBN异二聚体肽（t（1/2）68 min，beta（+）89%，EC 11%），Ga-68-NOTA-RGD-BBN的双重受体靶向性和肿瘤诊断价值。通过放射性配体竞争结合试验研究双受体结合亲和力。评价Ga-68-NOTA-RGD-BBN的体外和体内双重受体靶向，并与Ga-68-NOTA-RGD和Ga-68-NOTA-BBN进行比较。NOTA-RGD-BBN具有分别与单体RGD和BBN相当的整合素α（V）β（3）和GRPR结合亲和力。通过在PC-3肿瘤模型中的阻断研究验证Ga-68-NOTA-RGD-BBN的双重受体靶向性质。Ga-68-NOTA-RGD-BBN显示出比Ga-68-NOTA-RGD和Ga-68-NOTA-BBN更高的肿瘤摄取。Ga-68-NOTA-RGD-BBN还可以对具有整合素或GRPR表达的肿瘤进行成像。Ga-68-NOTA-RGD-BBN在体外和体内均表现出双重受体靶向性质。Ga-68-NOTA-RGD-BBN具有合成方便、比活性高、肿瘤摄取率高等优点，值得进一步研究用于临床肿瘤显像。
Radiolabeled Arg-Gly-Asp (RGD) and bombesin (BBN) peptide analogs have been extensively investigated for the imaging of tumor integrin alpha(v)beta(3) and gastrin-releasing peptide receptor (GRPR) expression, respectively. Recently, we designed and synthesized a RGD-BBN heterodimeric peptide from c(RGDyK) and BBN(7-14) through a glutamate linker. The goal of this study was to investigate the dual receptor-targeting property and tumor diagnostic value of RGD-BBN heterodimeric peptide labeled with generator-eluted Ga-68 (t(1/2) 68 min, beta(+) 89% and EC 11%), Ga-68-NOTA-RGD-BBN.RGD-BBN heterodimer was conjugated with 1,4,7-triazacyclononanetriacetic acid (NOTA) and labeled with Ga-68. The dual receptor binding affinity was investigated by a radioligand competition binding assay. The in vitro and in vivo dual receptor targeting of Ga-68-NOTA-RGD-BBN was evaluated and compared with that of Ga-68-NOTA-RGD and Ga-68-NOTA-BBN.NOTA-RGD-BBN had integrin alpha(v)beta(3) and GRPR binding affinities comparable to those of the monomeric RGD and BBN, respectively. The dual receptor targeting property of Ga-68-NOTA-RGD-BBN was validated by blocking studies in a PC-3 tumor model. Ga-68-NOTA-RGD-BBN showed higher tumor uptake than Ga-68-NOTA-RGD and Ga-68-NOTA-BBN. Ga-68-NOTA-RGD-BBN can also image tumors with either integrin or GRPR expression.Ga-68-NOTA-RGD-BBN exhibited dual receptor targeting properties both in vitro and in vivo. The favorable characterizations of Ga-68-NOTA-RGD-BBN such as convenient synthesis, high specific activity, and high tumor uptake, warrant its further investigation for clinical cancer imaging.