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Imaging Integrin αvβ3 and NRP-1 Positive Gliomas with a Novel Fluorine-18 Labeled RGD-ATWLPPR Heterodimeric Peptide Probe

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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 αvβ3 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 αvβ3 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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Acknowledgments

This study was supported by grant no. 81101066 from National Nature Science Foundation of China.

Conflict of Interest

The authors declare that they have no conflict of interest.

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Authors and Affiliations

  1. Department of Nuclear Medicine, Xiamen Cancer Center, The First Affiliated Hospital of Xiamen University, 55 Zhenhai Rd., Xiamen, 361003, China

    Hua Wu & Haojun Chen

  2. Department of Radiology and Medical Imaging, University of Virginia, Charlotteville, VA, 22908, USA

    Dongfeng Pan

  3. Department of Nuclear Medicine, Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, 200092, China

    Yufei Ma & Sheng Liang

  4. College of Life Science and Technology, Huazhong University of Science and Technology, Wuhan, 430074, China

    Ying Wan

  5. Key Laboratory of Health Technology Assessment of Fujian Province University, State key Laboratory of Molecular Vaccinology and Molecular Diagnostics, School of Public Health, Xiamen University, Xiamen, 361102, China

    Ya Fang

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  1. Hua Wu
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  2. Haojun Chen
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  3. Dongfeng Pan
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  4. Yufei Ma
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Corresponding author

Correspondence to Hua Wu.

Additional information

Hua Wu and Haojun Chen contributed equally to this work.

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Wu, H., Chen, H., Pan, D. et al. Imaging Integrin αvβ3 and NRP-1 Positive Gliomas with a Novel Fluorine-18 Labeled RGD-ATWLPPR Heterodimeric Peptide Probe. Mol Imaging Biol 16, 781–792 (2014). https://doi.org/10.1007/s11307-014-0761-0

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  • DOI: https://doi.org/10.1007/s11307-014-0761-0

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