Specific imaging of VEGF-A expression with radiolabeled anti-VEGF monoclonal antibody.
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.
Stollman
Thamar H
TH
Department of Surgery, Radboud University Nijmegen Medical Center, 6500 HB Nijmegen, The Netherlands.
Scheer
Marian G W
MG
Leenders
William P J
WP
Verrijp
Kiek C N
KC
Soede
Annemieke C
AC
Oyen
Wim J G
WJ
Ruers
Theo J M
TJ
Boerman
Otto C
OC
D020533:Angiogenesis Inhibitors; D000818:Animals; D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000068258:Bevacizumab; D003110:Colonic Neoplasms / Q000737:chemistry* / Q000000981:diagnostic imaging / Q000473:pathology; D006801:Humans; D007124:Immunoenzyme Techniques; D007205:Indium Radioisotopes; D007457:Iodine Radioisotopes; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D011877:Radionuclide Imaging; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014018:Tissue Distribution; D042461:Vascular Endothelial Growth Factor A / Q000032:analysis*; D023041:Xenograft Model Antitumor Assays
D020533:Angiogenesis Inhibitors; D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D007205:Indium Radioisotopes; D007457:Iodine Radioisotopes; D012333:RNA, Messenger; D042461:Vascular Endothelial Growth Factor A; C467480:vascular endothelial growth factor A, mouse; D000068258:Bevacizumab