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European Journal of Nuclear Medicine and Molecular Imaging

Published in:

01-06-2009 | Original Article

⁶⁸Ga-labeled cyclic RGD dimers with Gly₃ and PEG₄ linkers: promising agents for tumor integrin α_vβ₃ PET imaging

Authors: Zhaofei Liu, Gang Niu, Jiyun Shi, Shuanglong Liu, Fan Wang, Shuang Liu, Xiaoyuan Chen

Published in: European Journal of Nuclear Medicine and Molecular Imaging | Issue 6/2009

Abstract

Purpose

Radiolabeled cyclic RGD (Arg-Gly-Asp) peptides have great potential for the early tumor detection and noninvasive monitoring of tumor metastasis and therapeutic response. ¹⁸F-labeled RGD analogs ([¹⁸F]-AH111585 and [¹⁸F]Galacto-RGD) have been investigated in clinical trials for positron emission tomography (PET) imaging of integrin expression in cancer patients. To develop new RGD radiotracers with higher tumor accumulation, improved in vivo kinetics, easy availability and low cost, we developed two new RGD peptides and labeled them with generator-eluted ⁶⁸Ga (t_1/2 = 68 min) for PET imaging of integrin α_vβ₃ expression in tumor xenograft models.

Materials and methods

The two new cyclic RGD dimers, E[PEG₄-c(RGDfK)]₂ (P₄-RGD2, PEG₄ = 15-amino-4,7,10,13-tetraoxapentadecanoic acid) and E[Gly₃-c(RGDfK)]₂ (G₃-RGD2, G₃ = Gly-Gly-Gly) were designed, synthesized and conjugated with 1,4,7-triazacyclononanetriacetic acid (NOTA) for ⁶⁸Ga labeling. The microPET imaging and biodistribution of the ⁶⁸Ga labeled RGD tracers were investigated in integrin α_vβ₃-positive tumor xenografts.

Results

The new RGD dimers with the Gly₃ and PEG₄ linkers showed higher integrin α_vβ₃ binding affinity than no-linker RGD dimer (RGD2). NOTA-G₃-RGD2 and NOTA-P₄-RGD2 could be labeled with ⁶⁸Ga within 30 min with higher purity (>98%) and specific activity (8.88–11.84 MBq/nmol). Both ⁶⁸Ga-NOTA-P₄-RGD2 and ⁶⁸Ga-NOTA-G₃-RGD2 exhibited significantly higher tumor uptake and tumor-to-normal tissue ratios than ⁶⁸Ga-NOTA-RGD2.

Conclusion

Because of their high affinity, high specificity and excellent pharmacokinetic properties, further investigation of the two novel RGD dimers for clinical PET imaging of integrin α_vβ₃ expression in cancer patients is warranted.

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Title: 68Ga-labeled cyclic RGD dimers with Gly3 and PEG4 linkers: promising agents for tumor integrin αvβ3 PET imaging
Authors: Zhaofei Liu
Gang Niu
Jiyun Shi
Shuanglong Liu
Fan Wang
Shuang Liu
Xiaoyuan Chen
Publication date: 01-06-2009
Publisher: Springer-Verlag
Published in: European Journal of Nuclear Medicine and Molecular Imaging / Issue 6/2009
Print ISSN: 1619-7070
Electronic ISSN: 1619-7089
DOI: https://doi.org/10.1007/s00259-008-1045-1

Keynote webinar | Spotlight on medication adherence

Springer Medicine

⁶⁸Ga-labeled cyclic RGD dimers with Gly₃ and PEG₄ linkers: promising agents for tumor integrin α_vβ₃ PET imaging

Abstract

Purpose

Materials and methods

Results

Conclusion

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Purpose

Materials and methods

Results

Conclusion

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