RT Journal Article
SR Electronic
T1 Bevacizumab treatment reduces targeting of anti-epidermal growth factor receptor and anti-insulin-like growth factor 1 receptor antibodies
JF Journal of Nuclear Medicine
JO J Nucl Med
FD Society of Nuclear Medicine
SP 12
OP 12
VO 53
IS supplement 1
A1 Heskamp, Sandra
A1 van Laarhoven, Hanneke
A1 Molkenboer-Kuenen, Janneke
A1 Oyen, Wim
A1 van der Graaf, Winette
A1 Boerman, Otto
YR 2012
UL http://jnm.snmjournals.org/content/53/supplement_1/12.abstract
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