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One-step radiosynthesis of 18F-AlF-NOTA-RGD2 for tumor angiogenesis PET imaging

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Abstract

Purpose

One of the major obstacles of the clinical translation of 18F-labeled arginine-glycine-aspartic acid (RGD) peptides has been the laborious multistep radiosynthesis. In order to facilitate the application of RGD-based positron emission tomography (PET) probes in the clinical setting we investigated in this study the feasibility of using the chelation reaction between Al18F and a macrocyclic chelator-conjugated dimeric RGD peptide as a simple one-step 18F labeling strategy for development of a PET probe for tumor angiogenesis imaging.

Methods

Dimeric cyclic peptide E[c(RGDyK)]2 (RGD2) was first conjugated with a macrocyclic chelator, 1,4,7-triazacyclononane-1,4,7-triacetic acid (NOTA), and the resulting bioconjugate NOTA-RGD2 was then radiofluorinated via Al18F intermediate to synthesize 18F-AlF-NOTA-RGD2. Integrin binding affinities of the peptides were assessed by a U87MG cell-based receptor binding assay using 125I-echistatin as the radioligand. The tumor targeting efficacy and in vivo profile of 18F-AlF-NOTA-RGD2 were further evaluated in a subcutaneous U87MG glioblastoma xenograft model by microPET and biodistribution.

Results

NOTA-RGD2 was successfully 18F-fluorinated with good yield within 40 min using the Al18F intermediate. The IC50 of 19F-AlF-NOTA-RGD2 was determined to be 46 ± 4.4 nM. Quantitative microPET studies demonstrated that 18F-AlF-NOTA-RGD2 showed high tumor uptake, fast clearance from the body, and good tumor to normal organ ratios.

Conclusion

NOTA-RGD2 bioconjugate has been successfully prepared and labeled with Al18F in one single step of radiosynthesis. The favorable in vivo performance and the short radiosynthetic route of 18F-AlF-NOTA-RGD2 warrant further optimization of the probe and the radiofluorination strategy to accelerate the clinical translation of 18F-labeled RGD peptides.

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Acknowledgement

This work was supported, in part, by NCI 5R01 CA119053 (ZC) and In vivo Cellular Molecular Imaging Center (ICMIC) grant P50 CA114747 (SSG).

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Authors and Affiliations

  1. Molecular Imaging Program at Stanford (MIPS), Canary Center at Stanford for Cancer Early Detection, Bio-X Program, Department of Radiology, Stanford University, 1201 Welch Road, Lucas Expansion, P095, Stanford, CA, 94305-5344, USA

    Shuanglong Liu, Hongguang Liu, Han Jiang, Yingding Xu & Zhen Cheng

  2. Department of Nuclear Medicine, Medical PET Center, Institute of Nuclear Medicine and Molecular Imaging, and the Second Affiliated Hospital of Zhejiang University School of Medicine, Key Laboratory of Medical Molecular Imaging of Zhejiang Province, Hangzhou, Zhejiang, 310009, China

    Han Jiang & Hong Zhang

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  1. Shuanglong Liu
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  2. Hongguang Liu
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  3. Han Jiang
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  4. Yingding Xu
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  5. Hong Zhang
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  6. Zhen Cheng
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Correspondence to Zhen Cheng.

Additional information

Shuanglong Liu and Hongguang Liu contributed equally to the work.

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Liu, S., Liu, H., Jiang, H. et al. One-step radiosynthesis of 18F-AlF-NOTA-RGD2 for tumor angiogenesis PET imaging. Eur J Nucl Med Mol Imaging 38, 1732–1741 (2011). https://doi.org/10.1007/s00259-011-1847-4

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  • DOI: https://doi.org/10.1007/s00259-011-1847-4

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