68Ga-DOTA-RGD peptide: biodistribution and binding into atherosclerotic plaques in mice | springermedicine.com

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European Journal of Nuclear Medicine and Molecular Imaging

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01-12-2009 | Original Article

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

Authors: 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

Published in: European Journal of Nuclear Medicine and Molecular Imaging | Issue 12/2009

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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^−/−ApoB^100/100 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.

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Title: 68Ga-DOTA-RGD peptide: biodistribution and binding into atherosclerotic plaques in mice
Authors: 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
Publication date: 01-12-2009
Publisher: Springer-Verlag
Published in: European Journal of Nuclear Medicine and Molecular Imaging / Issue 12/2009
Print ISSN: 1619-7070
Electronic ISSN: 1619-7089
DOI: https://doi.org/10.1007/s00259-009-1220-z

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