Specific imaging of VEGF-A expression with radiolabeled anti-VEGF monoclonal antibody

T. Stollman, M. Scheer, W. Leenders, K. Verrijp, A. Soede, W. Oyen, T. Ruers and O. Boerman

Department of Surgery, Radboud University Nijmegen Medical Center, 6500 HB Nijmegen, The Netherlands.
May, 2008



Vascular endothelial growth factor-A (VEGF-A) is one of the most important angiogenic factors. Here, we studied in a nude mouse model whether the expression of VEGF-A in a tumor could be imaged with a radiolabeled anti-VEGF antibody. The humanized anti-VEGF-A antibody A.4.6.1. (bevacizumab), which is reactive with all VEGF-A isoforms, was radiolabeled with In-111 or with I-125. The accumulation of the radiolabeled antibodies in VEGF-A expressing tumors (LS174T) in nude mice was examined in biodistribution studies and by gamma camera imaging. The uptake of the In-111-bevacizumab in the tumor at 3 days p.i. was significantly higher than that of I-125-bevacizumab (19.4 +/- 7.0 \%ID/g vs. 9.6 +/- 3.3 \%ID/g, p = 0.04). Coinjection of an excess unlabeled antibody resulted in a significant decrease in radioactivity concentration in the tumor (<2.9 +/- 1.9 \%ID/g, p < 0.005), indicating VEGF-mediated antibody uptake. Highest uptake in the tumor was observed at relatively low antibody protein doses (<3 microg) (20-25 \%ID/g). VEGF-A-expressing tumors could be clearly visualized on planar scintigraphic images from 24-hr post injection onwards. In conclusion, VEGF-A expression in tumors can be visualized specifically with radiolabeled anti-VEGF-A-mAb.