Document Detail


Bevacizumab reduces tumor targeting of anti-epidermal growth factor and anti-insulin-like growth factor 1 receptor antibodies.
MedLine Citation:
PMID:  23335047     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
Bevacizumab (anti-VEGF) and cetuximab (anti-EGFR) are approved antibodies for treatment of cancer. However, in advanced colorectal cancer, the combination fails to improve survival. As the reason for the lack of activity is unknown, this study aims to determine the effect of bevacizumab on targeting of anti-EGFR and IGF-1R antibodies in tumors with SPECT/CT imaging. Mice with subcutaneous EGFR and IGF-1R-expressing SUM149 xenografts received a single dose of bevacizumab (10 mg/kg) or saline. After four days, mice were injected with radiolabeled cetuximab or R1507, an anti-IGF-1R antibody. A control group received a radiolabeled irrelevant IgG (hLL2). Three days later, SPECT/CT images were acquired and mice were dissected to determine the concentration of antibodies in the tissues. Tumors were analyzed immunohistochemically to determine vascular density (CD34), VEGF, EGFR and IGF-1R expression. SPECT/CT imaging revealed that bevacizumab treatment significantly reduced tumor targeting of radiolabeled cetuximab by 40% from 33.1 ± 1.1 %ID/g to 19.8 ± 5.7 %ID/g (p = 0.009) for untreated and bevacizumab treated tumors, respectively. A similar effect was found for (111) In-R1507: tumor targeting of R1507 decreased by 35%. No significant differences in tumor uptake were observed in mice that received an irrelevant IgG. Uptake in normal organs was not altered by bevacizumab. Immunohistochemical analysis showed that vascular density decreased with 43%, while EGFR and IGF-1R expression was unaltered. In conclusion, bevacizumab treatment significantly reduces tumor targeting of anti-EGFR and anti-IGF-1R antibodies. This emphasizes the importance of timing and sequencing of bevacizumab in combination with other antibodies.
Authors:
Sandra Heskamp; Otto C Boerman; Janneke D M Molkenboer-Kuenen; Wim J G Oyen; Winette T A van der Graaf; Hanneke W M van Laarhoven
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2013-1-21
Journal Detail:
Title:  International journal of cancer. Journal international du cancer     Volume:  -     ISSN:  1097-0215     ISO Abbreviation:  Int. J. Cancer     Publication Date:  2013 Jan 
Date Detail:
Created Date:  2013-1-21     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0042124     Medline TA:  Int J Cancer     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Copyright Information:
Copyright © 2013 UICC.
Affiliation:
Department of Medical Oncology, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands; Department of Nuclear Medicine, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands. s.heskamp@nucmed.umcn.nl.
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