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EJNMMI Research
Published in: EJNMMI Research 1/2017

Open Access 01-12-2017 | Original research

Monitoring response to anti-angiogenic mTOR inhibitor therapy in vivo using 111In-bevacizumab

Authors: Neel Patel, Sarah Able, Danny Allen, Emmanouil Fokas, Bart Cornelissen, Fergus V. Gleeson, Adrian L. Harris, Katherine A. Vallis

Published in: EJNMMI Research | Issue 1/2017

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Abstract

Background

The ability to image vascular endothelial growth factor (VEGF) could enable prospective, non-invasive monitoring of patients receiving anti-angiogenic therapy. This study investigates the specificity and pharmacokinetics of 111In-bevacizumab binding to VEGF and its use for assessing response to anti-angiogenic therapy with rapamycin.
Specificity of 111In-bevacizumab binding to VEGF was tested in vitro with unmodified radiolabelled bevacizumab in competitive inhibition assays. Uptake of 111In-bevacizumab in BALB/c nude mice bearing tumours with different amounts of VEGF expression was compared to that of isotype-matched control antibody (111In-IgG1κ) with an excess of unlabelled bevacizumab. Intratumoural VEGF was evaluated using ELISA and Western blot analysis. The effect of anti-angiogenesis therapy was tested by measuring tumour uptake of 111In-bevacizumab in comparison to 111In-IgG1κ following administration of rapamycin to mice bearing FaDu xenografts. Uptake was measured using gamma counting of ex vivo tumours and effect on vasculature by using anti-CD31 microscopy.

Results

Specific uptake of 111In-bevacizumab in VEGF-expressing tumours was observed. Rapamycin led to tumour growth delay associated with increased relative vessel size (8.5 to 10.3, P = 0.045) and decreased mean relative vessel density (0.27 to 0.22, P = 0.0015). Rapamycin treatment increased tumour uptake of 111In-bevacizumab (68%) but not 111In-IgGκ and corresponded with increased intratumoural VEGF165.

Conclusions

111In-bevacizumab accumulates specifically in VEGF-expressing tumours, and changes after rapamycin therapy reflect changes in VEGF expression. Antagonism of mTOR may increase VEGF in vivo, and this new finding provides the basis to consider combination studies blocking both pathways and a way to monitor effects.
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Metadata
Title
Monitoring response to anti-angiogenic mTOR inhibitor therapy in vivo using 111In-bevacizumab
Authors
Neel Patel
Sarah Able
Danny Allen
Emmanouil Fokas
Bart Cornelissen
Fergus V. Gleeson
Adrian L. Harris
Katherine A. Vallis
Publication date
01-12-2017
Publisher
Springer Berlin Heidelberg
Published in
EJNMMI Research / Issue 1/2017
Electronic ISSN: 2191-219X
DOI
https://doi.org/10.1186/s13550-017-0297-9

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