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European Journal of Nuclear Medicine and Molecular Imaging

Published in:

01-02-2007 | Original article

Improved targeting of the α_vβ₃ integrin by multimerisation of RGD peptides

Authors: Ingrid Dijkgraaf, John A. W. Kruijtzer, Shuang Liu, Annemieke C. Soede, Wim J. G. Oyen, Frans H. M. Corstens, Rob M. J. Liskamp, Otto C. Boerman

Published in: European Journal of Nuclear Medicine and Molecular Imaging | Issue 2/2007

Abstract

Purpose

The integrin α_vβ₃ is expressed on sprouting endothelial cells and on various tumour cell types. Due to the restricted expression of α_vβ₃ in tumours, α_vβ₃ is considered a suitable receptor for tumour targeting. In this study the α_vβ₃ binding characteristics of an ¹¹¹In-labelled monomeric, dimeric and tetrameric RGD analogue were compared.

Methods

A monomeric (E-c(RGDfK)), dimeric (E-[c(RGDfK)]₂), and tetrameric (E{E[c(RGDfK)]₂}₂) RGD peptide were synthesised, conjugated with DOTA and radiolabelled with ¹¹¹In. In vitro α_vβ₃ binding characteristics were determined in a competitive binding assay. In vivo α_vβ₃ targeting characteristics of the compounds were assessed in mice with SK-RC-52 xenografts.

Results

The IC₅₀ values for DOTA-E-c(RGDfK), DOTA-E-[c(RGDfK)]₂, and DOTA-E{E[c(RGDfK)]₂}₂were 120 nM, 69.9 nM and 19.6 nM, respectively. At all time points, the tumour uptake of the dimer was significantly higher as compared to that of the monomer. At 8 h p.i., tumour uptake of the tetramer (7.40±1.12%ID/g) was significantly higher than that of the monomer (2.30±0.34%ID/g), p<0.001, and the dimer (5.17±1.22%ID/g), p<0.05. At 24 h p.i., the tumour uptake was significantly higher for the tetramer (6.82±1.41%ID/g) than for the dimer (4.22±0.96%ID/g), p<0.01, and the monomer (1.90±0.29%ID/g), p<0.001.

Conclusion

Multimerisation of c(RGDfK) resulted in enhanced affinity for α_vβ₃ as determined in vitro. Tumour uptake of a tetrameric RGD peptide was significantly higher than that of the monomeric and dimeric analogues, presumably owing to the enhanced statistical likelihood for rebinding to α_vβ₃.

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Title: Improved targeting of the αvβ3 integrin by multimerisation of RGD peptides
Authors: Ingrid Dijkgraaf
John A. W. Kruijtzer
Shuang Liu
Annemieke C. Soede
Wim J. G. Oyen
Frans H. M. Corstens
Rob M. J. Liskamp
Otto C. Boerman
Publication date: 01-02-2007
Publisher: Springer-Verlag
Published in: European Journal of Nuclear Medicine and Molecular Imaging / Issue 2/2007
Print ISSN: 1619-7070
Electronic ISSN: 1619-7089
DOI: https://doi.org/10.1007/s00259-006-0180-9

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Improved targeting of the α_vβ₃ integrin by multimerisation of RGD peptides

Abstract

Purpose

Methods

Results

Conclusion

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Purpose

Methods

Results

Conclusion

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