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68Ga-DOTA-RGD peptide: biodistribution and binding into atherosclerotic plaques in mice

  • Johanna Haukkala
  • Iina Laitinen
  • Pauliina Luoto
  • Peter Iveson
  • Ian Wilson
  • Hege Karlsen
  • Alan Cuthbertson
  • Jukka Laine
  • Pia Leppänen
  • Seppo Ylä-Herttula
  • Juhani Knuuti
  • Anne Roivainen
Original Article

Abstract

Purpose

Increased expression of αvβ3/αvβ5 integrin is involved in angiogenesis and the inflammatory process in atherosclerotic plaques. The novel 68Ga-DOTA-RGD peptide binds with high affinity to αvβ3/αvβ5 integrin. The aim of this study was to investigate the uptake of the 68Ga-DOTA-RGD peptide in atherosclerotic plaques.

Methods

Uptake of intravenously administered 68Ga-DOTA-RGD peptide was studied ex vivo in excised tissue samples and aortic sections of LDLR−/−ApoB100/100 atherosclerotic mice. The uptake of the tracer in aortic cryosections was examined by using digital autoradiography. Subsequently, the autoradiographs were combined with histological and immunohistological analysis of the sections.

Results

DOTA-RGD peptide was successfully labelled with the generator-produced 68Ga. The tracer had reasonably good specific radioactivity (8.7 ± 1.1 GBq/μmol) and was quite stable in vivo. According to ex vivo biodistribution results, 68Ga-DOTA-RGD was cleared rapidly from the blood circulation and excreted through the kidneys to the urine with high radioactivity in the intestine, lungs, spleen and liver. Autoradiography results showed significantly higher uptake of 68Ga-DOTA-RGD peptide in the atherosclerotic plaques compared to healthy vessel wall (mean ratio ± SD 1.4 ± 0.1, p = 0.0004).

Conclusion

We observed that 68Ga-DOTA-RGD is accumulated into the plaques of atherosclerotic mice. However, this data only shows the feasibility of the approach, while the clinical significance still remains to be proven. Further studies are warranted to assess the uptake of this tracer into human atherosclerotic plaques.

Keywords

Atherosclerosis Plaque 68Ga αvβ3/αvβ5 integrin RGD PET 

Notes

Acknowledgements

This study was conducted within the Finnish Centre of Excellence in Molecular Imaging in Cardiovascular and Metabolic Research, supported by the Academy of Finland, University of Turku, Turku University Hospital and Åbo Akademi University. The work was funded by the Finnish Foundation for Cardiovascular Research and Drug Discovery Graduate School of the University of Turku. The authors would like to thank Erja Mäntysalo for excellent assistance in animal experiments, Erica Nyman for performing tissue sectioning and immunostainings, Irina Lisinen for providing expertise in statistical tests, Sanna Hellberg for image processing, and Henri Sipilä for assistance in 68Ga-labelling and HPLC analyses.

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Copyright information

© Springer-Verlag 2009

Authors and Affiliations

  • Johanna Haukkala
    • 1
  • Iina Laitinen
    • 1
  • Pauliina Luoto
    • 1
  • Peter Iveson
    • 2
  • Ian Wilson
    • 2
  • Hege Karlsen
    • 3
  • Alan Cuthbertson
    • 3
  • Jukka Laine
    • 4
  • Pia Leppänen
    • 5
  • Seppo Ylä-Herttula
    • 5
  • Juhani Knuuti
    • 1
  • Anne Roivainen
    • 1
    • 6
  1. 1.Turku PET CentreUniversity of TurkuTurkuFinland
  2. 2.GE Healthcare BiosciencesMedical DiagnosticsLondonUK
  3. 3.GE Healthcare MDx ResearchOsloNorway
  4. 4.Department of PathologyTurku University HospitalTurkuFinland
  5. 5.A.I. Virtanen InstituteUniversity of KuopioKuopioFinland
  6. 6.Turku Centre for Disease ModellingUniversity of TurkuTurkuFinland

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