, Volume 36, Issue 9, pp 1483-1494
Date: 10 Apr 2009

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

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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.