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European Journal of Nuclear Medicine and Molecular Imaging

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01-06-2008 | Original article

⁶⁸Ga-labeled multimeric RGD peptides for microPET imaging of integrin α_vβ₃ expression

Authors: Zi-Bo Li, Kai Chen, Xiaoyuan Chen

Published in: European Journal of Nuclear Medicine and Molecular Imaging | Issue 6/2008

Abstract

Purpose

We and others have reported that ¹⁸F- and ⁶⁴Cu-labeled arginine–glycine–aspartate (RGD) peptides allow positron emission tomography (PET) quantification of integrin α_vβ₃ expression in vivo. However, clinical translation of these radiotracers is partially hindered by the necessity of cyclotron facility to produce the PET isotopes. Generator-based PET isotope ⁶⁸Ga, with a half-life of 68 min and 89% positron emission, deserves special attention because of its independence of an onsite cyclotron. The goal of this study was to investigate the feasibility of ⁶⁸Ga-labeled RGD peptides for tumor imaging.

Methods

Three cyclic RGD peptides, c(RGDyK) (RGD1), E[c(RGDyK)]₂ (RGD2), and E{E[c(RGDyK)]₂}₂ (RGD4), were conjugated with macrocyclic chelator 1,4,7-triazacyclononane-1,4,7-triacetic acid (NOTA) and labeled with ⁶⁸Ga. Integrin affinity and specificity of the peptide conjugates were assessed by cell-based receptor binding assay, and the tumor targeting efficacy of ⁶⁸Ga-labeled RGD peptides was evaluated in a subcutaneous U87MG glioblastoma xenograft model.

Results

U87MG cell-based receptor binding assay using ¹²⁵I-echistatin as radioligand showed that integrin affinity followed the order of NOTA–RGD4 > NOTA–RGD2 > NOTA–RGD1. All three NOTA conjugates allowed nearly quantitative ⁶⁸Ga-labeling within 10 min (12–17 MBq/nmol). Quantitative microPET imaging studies showed that ⁶⁸Ga-NOTA–RGD4 had the highest tumor uptake but also prominent activity accumulation in the kidneys. ⁶⁸Ga-NOTA–RGD2 had higher tumor uptake (e.g., 2.8 ± 0.1%ID/g at 1 h postinjection) and similar pharmacokinetics (4.4 ± 0.4 tumor/muscle ratio, 2.0 ± 0.1 tumor/liver ratio, and 1.1 ± 0.1 tumor/kidney ratio) compared with ⁶⁸Ga-NOTA–RGD1.

Conclusions

The dimeric RGD peptide tracer ⁶⁸Ga-NOTA–RGD2 with good tumor uptake and favorable pharmacokinetics warrants further investigation for potential clinical translation to image integrin α_vβ₃.

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Title: 68Ga-labeled multimeric RGD peptides for microPET imaging of integrin αvβ3 expression
Authors: Zi-Bo Li
Kai Chen
Xiaoyuan Chen
Publication date: 01-06-2008
Publisher: Springer-Verlag
Published in: European Journal of Nuclear Medicine and Molecular Imaging / Issue 6/2008
Print ISSN: 1619-7070
Electronic ISSN: 1619-7089
DOI: https://doi.org/10.1007/s00259-007-0692-y

Keynote webinar | Spotlight on medication adherence

Springer Medicine

⁶⁸Ga-labeled multimeric RGD peptides for microPET imaging of integrin α_vβ₃ expression

Abstract

Purpose

Methods

Results

Conclusions

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Purpose

Methods

Results

Conclusions

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