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

Original Article

DOI: 10.1007/s00259-009-1123-z

Cite this article as:
Liu, Z., Niu, G., Wang, F. et al. Eur J Nucl Med Mol Imaging (2009) 36: 1483. doi:10.1007/s00259-009-1123-z



Radiolabeled Arg-Gly-Asp (RGD) and bombesin (BBN) peptide analogs have been extensively investigated for the imaging of tumor integrin αvβ3 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 68Ga (t1/2 68 min, β+ 89% and EC 11%), 68Ga-NOTA-RGD-BBN.


RGD-BBN heterodimer was conjugated with 1,4,7-triazacyclononanetriacetic acid (NOTA) and labeled with 68Ga. The dual receptor binding affinity was investigated by a radioligand competition binding assay. The in vitro and in vivo dual receptor targeting of 68Ga-NOTA-RGD-BBN was evaluated and compared with that of 68Ga-NOTA-RGD and 68Ga-NOTA-BBN.


NOTA-RGD-BBN had integrin αvβ3 and GRPR binding affinities comparable to those of the monomeric RGD and BBN, respectively. The dual receptor targeting property of 68Ga-NOTA-RGD-BBN was validated by blocking studies in a PC-3 tumor model. 68Ga-NOTA-RGD-BBN showed higher tumor uptake than 68Ga-NOTA-RGD and 68Ga-NOTA-BBN. 68Ga-NOTA-RGD-BBN can also image tumors with either integrin or GRPR expression.


68Ga-NOTA-RGD-BBN exhibited dual receptor targeting properties both in vitro and in vivo. The favorable characterizations of 68Ga-NOTA-RGD-BBN such as convenient synthesis, high specific activity, and high tumor uptake, warrant its further investigation for clinical cancer imaging.


Integrin αvβ3 Gastrin releasing peptide receptor (GRPR) RGD peptide Bombesin Peptide heterodimer Positron emission tomography (PET) Gallium-68 (68Ga) 

Supplementary material

259_2009_1123_MOESM1_ESM.doc (24.6 mb)
Suppl. Fig. 1Immunofluorescent staining of gastrin releasing peptide receptor (GRPR), human integrin αvβv, and murine integrin β3 for normal organs of nude mice (DOC 25189 kb)

Copyright information

© Springer-Verlag 2009

Authors and Affiliations

  • Zhaofei Liu
    • 1
    • 2
  • Gang Niu
    • 1
  • Fan Wang
    • 2
  • Xiaoyuan Chen
    • 1
  1. 1.The Molecular Imaging Program at Stanford (MIPS), Department of Radiology and Bio-X ProgramStanford University School of MedicineStanfordUSA
  2. 2.Medical Isotopes Research CenterPeking UniversityBeijingChina