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18F-Labeled Galacto and PEGylated RGD Dimers for PET Imaging of αvβ3 Integrin Expression

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Abstract

Purpose

In vivo imaging of αvβ3 has important diagnostic and therapeutic applications. 18F-Galacto-arginine–glycine–aspartic acid (RGD) has been developed for positron emission tomography (PET) imaging of integrin αvβ3 expression and is now being tested on humans. Dimerization and multimerization of cyclic RGD peptides have been reported to improve the integrin αvβ3-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 αvβ3 imaging.

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Acknowledgment

This work was supported, in part, by the National Cancer Institute (R01 120188, R01 CA119053, R21 CA121842, P50 CA114747, U54 CA119367, and R24 CA93862). We thank the cyclotron team at Stanford University for 18F-F− production.

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Authors and Affiliations

  1. Molecular Imaging Program at Stanford (MIPS), Department of Radiology and Bio-X Program, Stanford University School of Medicine, 1201 Welch Rd., P095, Stanford, CA, 94305-5484, USA

    Shuanglong Liu, Zhaofei Liu, Kai Chen, Yongjun Yan, Frederick T. Chin & Xiaoyuan Chen

  2. Department of Nuclear Medicine, Klinikum Rechts der Isar, Technische Universität München, Munich, Germany

    Petra Watzlowik & Hans-Jürgen Wester

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  1. Shuanglong Liu
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  2. Zhaofei Liu
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  3. Kai Chen
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  7. Frederick T. Chin
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  8. Xiaoyuan Chen
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Correspondence to Xiaoyuan Chen.

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Shuanglong Liu and Zhaofei Liu contributed equally to this work.

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Liu, S., Liu, Z., Chen, K. et al. 18F-Labeled Galacto and PEGylated RGD Dimers for PET Imaging of αvβ3 Integrin Expression. Mol Imaging Biol 12, 530–538 (2010). https://doi.org/10.1007/s11307-009-0284-2

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