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European Journal of Nuclear Medicine and Molecular Imaging

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01-11-2007 | Molecular Imaging

¹⁸F-labeled mini-PEG spacered RGD dimer (¹⁸F-FPRGD2): synthesis and microPET imaging of α_vβ₃ integrin expression

Authors: Zhanhong Wu, Zi-Bo Li, Weibo Cai, Lina He, Frederick T. Chin, Fang Li, Xiaoyuan Chen

Published in: European Journal of Nuclear Medicine and Molecular Imaging | Issue 11/2007

Abstract

Purpose

We have previously reported that ¹⁸F-FB-E[c(RGDyK)]₂ (¹⁸F-FRGD2) allows quantitative PET imaging of integrin α_vβ₃ expression. However, the potential clinical translation was hampered by the relatively low radiochemical yield. The goal of this study was to improve the radiolabeling yield, without compromising the tumor targeting efficiency and in vivo kinetics, by incorporating a hydrophilic bifunctional mini-PEG spacer.

Methods

¹⁸F-FB-mini-PEG-E[c(RGDyK)]₂ (¹⁸F-FPRGD2) was synthesized by coupling N-succinimidyl-4-¹⁸F-fluorobenzoate (¹⁸F-SFB) with NH₂-mini-PEG-E[c(RGDyK)]₂ (denoted as PRGD2). In vitro receptor binding affinity, metabolic stability, and integrin α_vβ₃ specificity of the new tracer ¹⁸F-FPRGD2 were assessed. The diagnostic value of ¹⁸F-FPRGD2 was evaluated in subcutaneous U87MG glioblastoma xenografted mice and in c-neu transgenic mice by quantitative microPET imaging studies.

Results

The decay-corrected radiochemical yield based on ¹⁸F-SFB was more than 60% with radiochemical purity of >99%. ¹⁸F-FPRGD2 had high receptor binding affinity, metabolic stability, and integrin α_vβ₃-specific tumor uptake in the U87MG glioma xenograft model comparable to those of ¹⁸F-FRGD2. The kidney uptake was appreciably lower for ¹⁸F-FPRGD2 compared with ¹⁸F-FRGD2 [2.0 ± 0.2%ID/g for ¹⁸F-FPRGD2 vs 3.0 ± 0.2%ID/g for ¹⁸F-FRGD2 at 1 h post injection (p.i.)]. The uptake in all the other organs except the urinary bladder was at background level. ¹⁸F-FPRGD2 also exhibited excellent tumor uptake in c-neu oncomice (3.6 ± 0.1%ID/g at 30 min p.i.).

Conclusion

Incorporation of a mini-PEG spacer significantly improved the overall radiolabeling yield of ¹⁸F-FPRGD2. ¹⁸F-FPRGD2 also had reduced renal uptake and similar tumor targeting efficacy as compared with ¹⁸F-FRGD2. Further testing and clinical translation of ¹⁸F-FPRGD2 are warranted.

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Title: 18F-labeled mini-PEG spacered RGD dimer (18F-FPRGD2): synthesis and microPET imaging of αvβ3 integrin expression
Authors: Zhanhong Wu
Zi-Bo Li
Weibo Cai
Lina He
Frederick T. Chin
Fang Li
Xiaoyuan Chen
Publication date: 01-11-2007
Publisher: Springer-Verlag
Published in: European Journal of Nuclear Medicine and Molecular Imaging / Issue 11/2007
Print ISSN: 1619-7070
Electronic ISSN: 1619-7089
DOI: https://doi.org/10.1007/s00259-007-0427-0

Keynote webinar | Spotlight on sleep in brain health

Springer Medicine

¹⁸F-labeled mini-PEG spacered RGD dimer (¹⁸F-FPRGD2): synthesis and microPET imaging of α_vβ₃ integrin expression

Abstract

Purpose

Methods

Results

Conclusion

Keynote webinar | Spotlight on sleep in brain health

Springer Medicine

Abstract

Purpose

Methods

Results

Conclusion

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