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European Journal of Nuclear Medicine and Molecular Imaging
Published in: European Journal of Nuclear Medicine and Molecular Imaging 1/2011

Open Access 01-01-2011 | Original Article

PET imaging of αvβ3 integrin expression in tumours with 68Ga-labelled mono-, di- and tetrameric RGD peptides

Authors: Ingrid Dijkgraaf, Cheng-Bin Yim, Gerben M. Franssen, Robert C. Schuit, Gert Luurtsema, Shuang Liu, Wim J. G. Oyen, Otto C. Boerman

Published in: European Journal of Nuclear Medicine and Molecular Imaging | Issue 1/2011

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Abstract

Purpose

Due to the restricted expression of αvβ3 in tumours, αvβ3 is considered a suitable receptor for tumour targeting. In this study the αvβ3-binding characteristics of 68Ga-labelled monomeric, dimeric and tetrameric RGD peptides were determined and compared with their 111In-labelled counterparts.

Methods

A monomeric (E-c(RGDfK)), a dimeric (E-[c(RGDfK)]2) and a tetrameric (E{E[c(RGDfK)]2}2) RGD peptide were synthesised, conjugated with DOTA and radiolabelled with 68Ga. In vitro αvβ3-binding characteristics were determined in a competitive binding assay. In vivo αvβ3-targeting characteristics of the compounds were assessed in mice with subcutaneously growing SK-RC-52 xenografts. In addition, microPET images were acquired using a microPET/CT scanner.

Results

The IC50 values for the Ga(III)-labelled DOTA-E-c(RGDfK), DOTA-E-[c(RGDfK)]2 and DOTA-E{E[c(RGDfK)]2}2 were 23.9 ± 1.22, 8.99 ± 1.20 and 1.74 ± 1.18 nM, respectively, and were similar to those of the In(III)-labelled mono-, di- and tetrameric RGD peptides (26.6 ± 1.15, 3.34 ± 1.16 and 1.80 ± 1.37 nM, respectively). At 2 h post-injection, tumour uptake of the 68Ga-labelled mono-, di- and tetrameric RGD peptides (3.30 ± 0.30, 5.24 ± 0.27 and 7.11 ± 0.67%ID/g, respectively) was comparable to that of their 111In-labelled counterparts (2.70 ± 0.29, 5.61 ± 0.85 and 7.32 ± 2.45%ID/g, respectively). PET scans were in line with the biodistribution data. On all PET scans, the tumour could be clearly visualised.

Conclusion

The integrin affinity and the tumour uptake followed the order of DOTA-tetramer > DOTA-dimer > DOTA-monomer. The 68Ga-labelled tetrameric RGD peptide has excellent characteristics for imaging of αvβ3 expression with PET.
Appendix
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Metadata
Title
PET imaging of αvβ3 integrin expression in tumours with 68Ga-labelled mono-, di- and tetrameric RGD peptides
Authors
Ingrid Dijkgraaf
Cheng-Bin Yim
Gerben M. Franssen
Robert C. Schuit
Gert Luurtsema
Shuang Liu
Wim J. G. Oyen
Otto C. Boerman
Publication date
01-01-2011
Publisher
Springer-Verlag
Published in
European Journal of Nuclear Medicine and Molecular Imaging / Issue 1/2011
Print ISSN: 1619-7070
Electronic ISSN: 1619-7089
DOI
https://doi.org/10.1007/s00259-010-1615-x

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