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01-10-2010 | Research Article

¹⁸F-Labeled Galacto and PEGylated RGD Dimers for PET Imaging of α_vβ₃ Integrin Expression

Authors: Shuanglong Liu, Zhaofei Liu, Kai Chen, Yongjun Yan, Petra Watzlowik, Hans-Jürgen Wester, Frederick T. Chin, Xiaoyuan Chen

Published in: Molecular Imaging and Biology | Issue 5/2010

Abstract

Purpose

In vivo imaging of α_vβ₃ has important diagnostic and therapeutic applications. ¹⁸F-Galacto-arginine–glycine–aspartic acid (RGD) has been developed for positron emission tomography (PET) imaging of integrin α_vβ₃ expression and is now being tested on humans. Dimerization and multimerization of cyclic RGD peptides have been reported to improve the integrin α_vβ₃-binding affinity due to the polyvalency effect. Here, we compared a number of new dimeric RGD peptide tracers with the clinically used ¹⁸F-galacto-RGD.

Procedures

RGD monomers and dimers were coupled with galacto or PEG₃ linkers, and labeled with ¹⁸F using 4-nitrophenyl 2-¹⁸F-fluoropropionate (¹⁸F-NFP) or N-succinimidyl 4-¹⁸F-fluorobenzoate as a prosthetic group. The newly developed tracers were evaluated by cell-based receptor-binding assay, biodistribution, and small-animal PET studies in a subcutaneous U87MG glioblastoma xenograft model.

Results

Starting with ¹⁸F-F⁻, the total reaction time for ¹⁸F-FP-SRGD2 and ¹⁸F-FP-PRGD2 is about 120 min. The decay-corrected radiochemical yields for ¹⁸F-FP-SRGD2 and ¹⁸F-FP-PRGD2 are 52 ± 9% and 80 ± 7% calculated from ¹⁸F-NFP. Noninvasive small-animal PET and direct tissue sampling experiments demonstrated that the dimeric RGD peptides had significantly higher tumor uptake as compared to ¹⁸F-galacto-RGD.

Conclusion

Dimeric RGD peptide tracers with relatively high tumor integrin-specific accumulation and favorable in vivo kinetics may have the potential to be translated into clinic for integrin α_vβ₃ imaging.

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Title: 18F-Labeled Galacto and PEGylated RGD Dimers for PET Imaging of αvβ3 Integrin Expression
Authors: Shuanglong Liu
Zhaofei Liu
Kai Chen
Yongjun Yan
Petra Watzlowik
Hans-Jürgen Wester
Frederick T. Chin
Xiaoyuan Chen
Publication date: 01-10-2010
Publisher: Springer-Verlag
Published in: Molecular Imaging and Biology / Issue 5/2010
Print ISSN: 1536-1632
Electronic ISSN: 1860-2002
DOI: https://doi.org/10.1007/s11307-009-0284-2

Keynote webinar | Spotlight on medication adherence

Springer Medicine

¹⁸F-Labeled Galacto and PEGylated RGD Dimers for PET Imaging of α_vβ₃ Integrin Expression

Abstract

Purpose

Procedures

Results

Conclusion

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Purpose

Procedures

Results

Conclusion

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