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

  • Shuanglong Liu
  • Hongguang Liu
  • Han Jiang
  • Yingding Xu
  • Hong Zhang
  • Zhen Cheng
Original Article



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.


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.


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.


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.


RGD dimer 18NOTA PET Aluminum fluoride Molecular imaging Integrin αvβ3 



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

Conflicts of interest



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Copyright information

© Springer-Verlag 2011

Authors and Affiliations

  • Shuanglong Liu
    • 1
  • Hongguang Liu
    • 1
  • Han Jiang
    • 1
    • 2
  • Yingding Xu
    • 1
  • Hong Zhang
    • 2
  • Zhen Cheng
    • 1
  1. 1.Molecular Imaging Program at Stanford (MIPS), Canary Center at Stanford for Cancer Early Detection, Bio-X Program, Department of RadiologyStanford UniversityStanfordUSA
  2. 2.Department of Nuclear Medicine, Medical PET CenterInstitute 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 ProvinceHangzhouChina

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