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Molecular Imaging and Biology

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01-12-2014 | Research Article

Imaging Integrin α_vβ₃ and NRP-1 Positive Gliomas with a Novel Fluorine-18 Labeled RGD-ATWLPPR Heterodimeric Peptide Probe

Authors: Hua Wu, Haojun Chen, Dongfeng Pan, Yufei Ma, Sheng Liang, Ying Wan, Ya Fang

Published in: Molecular Imaging and Biology | Issue 6/2014

Abstract

Purpose

Radiolabeled Arg-Gly-Asp (RGD) and Ala-Thr-Trp-Leu-Pro-Pro-Arg (ATWLPPR) peptide analogs have received interests for their capability to serve as radiopharmaceuticals for imaging integrin α_vβ₃ and Neuropilin-1 (NRP-1) positive tumors, respectively. In this study, we developed a RGD-ATWLPPR heterodimeric peptide which contained both RGD and ATWLPPR motifs in one molecular probe. The aim of this study was to investigate the dual receptor-targeting property and tumor diagnostic value of RGD-ATWLPPR heterodimeric peptide labeled with fluorine-18 (F-18).

Procedures

A RGD-ATWLPPR heterodimer was synthesized from c(RGDyK) and ATWLPPR through a glutamate linker. The peptide was radiolabeled by reacting the [¹⁸F]fluoride–aluminum complex with the cyclic chelator, 1,4,7-triazacyclononane-1,4,7-triacetic acid (NOTA). The receptor-binding characteristics and tumor-targeting efficacy of [¹⁸F]FAl-NOTA-RGD-ATWLPPR were tested in vitro and in vivo.

Results

RGD-ATWLPPR had affinity for both integrin α_vβ₃ and NRP-1 in vitro. [¹⁸F]FAl-NOTA-RGD-ATWLPPR displayed significantly higher tumor uptake than [¹⁸F]FAl-NOTA-RGD and [¹⁸F]FAl-NOTA-ATWLPPR, both in vitro and in vivo. The uptake of the F-18 labeled heterodimer by an U87MG tumor was inhibited only partially in the presence of an excess amount of unlabeled RGD or ATWLPPR but was blocked completely in the presence of both RGD and ATWLPPR. Compared with the monomeric RGD and ATWLPPR peptides, [¹⁸F]FAl-NOTA-RGD-ATWLPPR showed improved in vivo pharmacokinetics, resulting in a more preferable imaging quality.

Conclusions

[¹⁸F]FAl-NOTA-RGD-ATWLPPR exhibited significantly improved receptor-targeting properties both in vitro and in vivo compared with the F-18 labeled RGD or ATWLPPR monomers. The improved targeting and localization exhibited by the RGD-ATWLPPR heterodimer provide a foundation for further investigations of its applicability in clinical tumor imaging.

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Title: Imaging Integrin αvβ3 and NRP-1 Positive Gliomas with a Novel Fluorine-18 Labeled RGD-ATWLPPR Heterodimeric Peptide Probe
Authors: Hua Wu
Haojun Chen
Dongfeng Pan
Yufei Ma
Sheng Liang
Ying Wan
Ya Fang
Publication date: 01-12-2014
Publisher: Springer US
Published in: Molecular Imaging and Biology / Issue 6/2014
Print ISSN: 1536-1632
Electronic ISSN: 1860-2002
DOI: https://doi.org/10.1007/s11307-014-0761-0

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Imaging Integrin α_vβ₃ and NRP-1 Positive Gliomas with a Novel Fluorine-18 Labeled RGD-ATWLPPR Heterodimeric Peptide Probe

Abstract

Purpose

Procedures

Results

Conclusions

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Purpose

Procedures

Results

Conclusions

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