68Ga-labeled NOTA-RGD-BBN peptide for dual integrin and GRPR-targeted tumor imaging

被引：124

作者：

Liu, Zhaofei ^{[1
,2
,3
]}

Niu, Gang ^{[1
,2
]}

Wang, Fan ^{[3
]}

Chen, Xiaoyuan ^{[1
,2
]}

机构：

[1] Stanford Univ, Dept Radiol, Sch Med, MIPS, Stanford, CA 94305 USA

[2] Stanford Univ, Bio X Program, Sch Med, Stanford, CA 94305 USA

[3] Peking Univ, Med Isotopes Res Ctr, Beijing 100191, Peoples R China

来源：

EUROPEAN JOURNAL OF NUCLEAR MEDICINE AND MOLECULAR IMAGING | 2009年 / 36卷 / 09期

关键词：

Integrin alpha(v)beta(3); Gastrin releasing peptide receptor (GRPR); RGD peptide; Bombesin; Peptide heterodimer; Positron emission tomography (PET); Gallium-68 (Ga-68); POSITRON-EMISSION-TOMOGRAPHY; ALPHA(V)BETA(3) EXPRESSION; BREAST-CANCER; RECEPTOR EXPRESSION; MDA-MB-435; CELLS; PET; MICROPET; BOMBESIN; HETERODIMER; MELANOMA;

D O I：

10.1007/s00259-009-1123-z

中图分类号：

R8 [特种医学]; R445 [影像诊断学];

学科分类号：

1002 ; 100207 ; 1009 ;

摘要：

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.

引用

页码：1483 / 1494

页数：12

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