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EJNMMI Research
Published in: EJNMMI Research 1/2014

Open Access 01-12-2014 | Original research

Visualization of angiogenesis during cancer development in the polyoma middle T breast cancer model: molecular imaging with (R)-[11C]PAQ

Authors: Erik Samén, Li Lu, Jan Mulder, Jan-Olov Thorell, Peter Damberg, Tetyana Tegnebratt, Lars Holmgren, Helene Rundqvist, Sharon Stone-Elander

Published in: EJNMMI Research | Issue 1/2014

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Abstract

Background

Vascular endothelial growth factor receptor 2 (VEGFR2) is a crucial mediator of tumour angiogenesis. High expression levels of the receptor have been correlated to poor prognosis in cancer patients. Reliable imaging biomarkers for stratifying patients for anti-angiogenic therapy could therefore be valuable for increasing treatment success rates. The aim of this study was to investigate the pharmacokinetics and angiogenesis imaging abilities of the VEGFR2-targeting positron emission tomography (PET) tracer (R)-[11C]PAQ.

Methods

(R)-[11C]PAQ was evaluated in the mouse mammary tumour virus-polyoma middle T (MMTV-PyMT) model of metastatic breast cancer. Mice at different stages of disease progression were imaged with (R)-[11C]PAQ PET, and results were compared to those obtained with [18 F]FDG PET and magnetic resonance imaging. (R)-[11C]PAQ uptake levels were also compared to ex vivo immunofluorescence analysis of tumour- and angiogenesis-specific biomarkers. Additional pharmacokinetic studies were performed in rat and mouse.

Results

A heterogeneous uptake of (R)-[11C]PAQ was observed in the tumorous mammary glands. Ex vivo analysis confirmed the co-localization of areas with high radioactivity uptake and areas with elevated levels of VEGFR2. In some animals, a high focal uptake was observed in the lungs. The lung uptake correlated to metastatic and angiogenic activity, but not to uptake of [18 F]FDG PET. The pharmacokinetic studies revealed a limited metabolism and excretion during the 1-h scan and a distribution of radioactivity mainly to the liver, kidneys and lungs. In rat, a high uptake was additionally observed in adrenal and parathyroid glands.

Conclusion

The results indicate that (R)-[11C]PAQ is a promising imaging biomarker for visualization of angiogenesis, based on VEGFR2 expression, in primary tumours and during metastasis development.
Appendix
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Metadata
Title
Visualization of angiogenesis during cancer development in the polyoma middle T breast cancer model: molecular imaging with (R)-[11C]PAQ
Authors
Erik Samén
Li Lu
Jan Mulder
Jan-Olov Thorell
Peter Damberg
Tetyana Tegnebratt
Lars Holmgren
Helene Rundqvist
Sharon Stone-Elander
Publication date
01-12-2014
Publisher
Springer Berlin Heidelberg
Published in
EJNMMI Research / Issue 1/2014
Electronic ISSN: 2191-219X
DOI
https://doi.org/10.1186/2191-219X-4-17

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