PT  - JOURNAL ARTICLE
AU  - Heskamp, Sandra
AU  - van Laarhoven, Hanneke
AU  - Molkenboer-Kuenen, Janneke
AU  - Oyen, Wim
AU  - van der Graaf, Winette
AU  - Boerman, Otto
TI  - Bevacizumab treatment reduces targeting of anti-epidermal growth factor receptor and anti-insulin-like growth factor 1 receptor antibodies
DP  - 2012 May 01
TA  - Journal of Nuclear Medicine
PG  - 12--12
VI  - 53
IP  - supplement 1
4099  - http://jnm.snmjournals.org/content/53/supplement_1/12.short
4100  - http://jnm.snmjournals.org/content/53/supplement_1/12.full
SO  - J Nucl Med2012 May 01; 53
AB  - 12 Objectives Bevacizumab and cetuximab are approved antibodies for treatment of metastasized colorectal cancer. However, the combination of bevacizumab and cetuximab does not improve progression free survival. This may be explained by the disruption of tumor vascularity by bevacizumab, thereby reducing targeting of other antibodies to the tumor. The aim of this study was to determine the effect of bevacizumab on the targeting of anti-EGFR and IGF-1R antibodies in tumors with SPECT/CT imaging. Methods Mice with subcutaneous EGFR and IGF-1R-expressing SUM149 xenografts were injected intraperitoneally with a single dose of bevacizumab (10 mg/kg). After four days, mice received an intravenous injection of 17 MBq 111In-labeled cetuximab, an anti-EGFR antibody, or R1507, an anti-IGF-1R antibody. A control group was injected with an irrelevant IgG. Three days later, SPECT/CT images were acquired and mice were dissected for ex vivo biodistribution. Tumors were analyzed immunohistochemically to determine vascular density (CD34), EGFR and IGF-1R expression. Results SPECT/CT imaging revealed that bevacizumab treatment reduced targeting of anti-EGFR and anti-IGF-1R antibodies by 42% and 35%, respectively. Ex vivo biodistribution showed that uptake of 111In-cetuximab in untreated tumors was 35.2 ± 1.6 %ID/g, compared with 19.7 ± 5.3 %ID/g for bevacizumab treated tumors (p = 0.009). A similar effect was observed for 111In-R1507. No significant differences in tumor uptake were observed in mice that received the irrelevant IgG. Immunohistochemical analysis showed that vascular density decreased with 40%, while EGFR and IGF-1R expression was unaltered. Conclusions Bevacizumab treatment can significantly reduce targeting of other antibodies to tumors. This underlines the importance of timing and sequencing of bevacizumab therapy in combination with other antibodies. Research Support NWO research grant (016.096.010) and Roch