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Quantitative PET Imaging of VEGF Receptor Expression

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Abstract

Purpose

Vascular endothelial growth factor (VEGF)/VEGF receptor (VEGFR) signaling pathway plays pivotal roles in regulating tumor angiogenesis. Quantitative positron emission tomography (PET) imaging of VEGFR will facilitate the planning of whether, and when, to start anti-angiogenic treatment and enable more robust and effective monitoring of such treatment.

Materials and methods

VEGF121 was conjugated with DOTA (1,4,7,10-tetra-azacylododecane N,N′,N′′,N′′′-tetraacetic acid) and then labeled with 64Cu for PET imaging of mice bearing different-sized human glioblastoma U87MG tumors (n = 15). Western blotting and immunofluorescence staining of tumor tissue was carried out to correlate with/validate the imaging results.

Results

The specific activity of 64Cu-DOTA-VEGF121 was 3.2 GBq/mg. The uptake of 64Cu-DOTA-VEGF121 in the tumor peaked when the tumor size was about 100–250 mm3. Both small and large tumors had lower tracer uptake indicating a narrow range of tumor size with high VEGFR-2 expression. All tumors had similarly low VEGFR-1 expression. Most importantly, the tumor uptake value obtained from PET imaging had good linear correlation with the relative tumor tissue VEGFR-2 expression as measured by Western blot, where r 2 equals 0.68 based on the PET uptake at 4 h post-injection. Histology of the frozen tumor tissue corroborates well with the imaging results.

Conclusion

The tumor uptake of 64Cu-DOTA-VEGF121 measured by small-animal PET imaging reflects tumor VEGFR-2 expression level in vivo. Such correlation may facilitate future treatment planning and treatment monitoring of cancer and potentially other angiogenesis-related diseases.

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Acknowledgments

This work was supported in part by the National Cancer Institute (NCI) (R01 CA119053, R21 CA121842, R21 CA102123, P50 CA114747, U54 CA119367, and R24 CA93862), the Department of Defense (DOD) (W81XWH-07-1-0374, W81XWH-04-1-0697, W81XWH-06-1-0665, W81XWH-06-1-0042), and Benedict Cassen Postdoctoral Fellowship (to W. Cai and Z-B Li) from the Education and Research Foundation of the Society of Nuclear Medicine.

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Authors and Affiliations

  1. The 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

    Kai Chen, Weibo Cai, Zi-Bo Li, Hui Wang & Xiaoyuan Chen

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  1. Kai Chen
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  2. Weibo Cai
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  3. Zi-Bo Li
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  5. Xiaoyuan Chen
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Correspondence to Xiaoyuan Chen.

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Kai Chen and Weibo Cai contributed equally to this work.

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Chen, K., Cai, W., Li, ZB. et al. Quantitative PET Imaging of VEGF Receptor Expression. Mol Imaging Biol 11, 15–22 (2009). https://doi.org/10.1007/s11307-008-0172-1

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  • DOI: https://doi.org/10.1007/s11307-008-0172-1

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