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European Journal of Nuclear Medicine and Molecular Imaging

Erschienen in:

01.12.2007 | Molecular Imaging

A new PET tracer specific for vascular endothelial growth factor receptor 2

verfasst von: Hui Wang, Weibo Cai, Kai Chen, Zi-Bo Li, Amir Kashefi, Lina He, Xiaoyuan Chen

Erschienen in: European Journal of Nuclear Medicine and Molecular Imaging | Ausgabe 12/2007

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Abstract

Purpose

Noninvasive positron emission tomography (PET) imaging of vascular endothelial growth factor receptor 2 (VEGFR-2) expression could be a valuable tool for evaluation of patients with a variety of malignancies, and particularly for monitoring those undergoing antiangiogenic therapies that block VEGF/VEGFR-2 function. The aim of this study was to develop a VEGFR-2-specific PET tracer.

Methods

The D63AE64AE67A mutant of VEGF₁₂₁ (VEGF_DEE) was generated by recombinant DNA technology. VEGF₁₂₁ and VEGF_DEE were purified and conjugated with DOTA for ⁶⁴Cu labeling. The DOTA conjugates were tested in vitro for VEGFR-2 specificity and functional activity. In vivo tumor targeting efficacy and pharmacokinetics of ⁶⁴Cu-labeled VEGF₁₂₁ and VEGF_DEE were compared using an orthotopic 4T1 murine breast tumor model. Blocking experiments, biodistribution studies, and immunofluorescence staining were carried out to confirm the noninvasive imaging results.

Results

Cell binding assay demonstrated that VEGF_DEE had about 20-fold lower VEGFR-1 binding affinity and only slightly lower VEGFR-2 binding affinity as compared with VEGF₁₂₁. MicroPET imaging studies revealed that both ⁶⁴Cu-DOTA-VEGF₁₂₁ and ⁶⁴Cu-DOTA-VEGF_DEE had rapid and prominent activity accumulation in VEGFR-2-expressing 4T1 tumors. The renal uptake of ⁶⁴Cu-DOTA-VEGF_DEE was significantly lower than that of ⁶⁴Cu-DOTA-VEGF₁₂₁ as rodent kidneys expressed high levels of VEGFR-1 based on immunofluorescence staining. Blocking experiments and biodistribution studies confirmed the VEGFR specificity of ⁶⁴Cu-DOTA-VEGF_DEE.

Conclusion

We have developed a VEGFR-2-specific PET tracer, ⁶⁴Cu-DOTA-VEGF_DEE. It has comparable tumor targeting efficacy to ⁶⁴Cu-DOTA-VEGF₁₂₁ but much reduced renal toxicity. This tracer may be translated into the clinic for imaging tumor angiogenesis and monitoring antiangiogenic treatment efficacy.

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Titel: A new PET tracer specific for vascular endothelial growth factor receptor 2
verfasst von: Hui Wang
Weibo Cai
Kai Chen
Zi-Bo Li
Amir Kashefi
Lina He
Xiaoyuan Chen
Publikationsdatum: 01.12.2007
Verlag: Springer-Verlag
Erschienen in: European Journal of Nuclear Medicine and Molecular Imaging / Ausgabe 12/2007
Print ISSN: 1619-7070
Elektronische ISSN: 1619-7089
DOI: https://doi.org/10.1007/s00259-007-0524-0

Live-Webinar "Urologie und Sexualmedizin in der Praxis"

Springer Medizin

A new PET tracer specific for vascular endothelial growth factor receptor 2

Abstract

Purpose

Methods

Results

Conclusion

Live-Webinar "Urologie und Sexualmedizin in der Praxis"

Springer Medizin

Abstract

Purpose

Methods

Results

Conclusion

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