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

Abstract

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.

• Authors: Thamar H Stollman, Marian G W Scheer, William P J Leenders, Kiek C N Verrijp, Annemieke C Soede, Wim J G Oyen, Theo J M Ruers, Otto C Boerman
• Journal: International journal of cancer (Int J Cancer) Vol. 122 Issue 10 Pg. 2310-4 (May 15 2008) ISSN: 1097-0215 [Electronic] United States
• PMID: 18240146 (Publication Type: Journal Article)
• Copyright: (c) 2008 Wiley-Liss, Inc.

Chemical References

• Angiogenesis Inhibitors
• Antibodies, Monoclonal
• Antibodies, Monoclonal, Humanized
• Indium Radioisotopes
• Iodine Radioisotopes
• RNA, Messenger
• Vascular Endothelial Growth Factor A
• vascular endothelial growth factor A, mouse
• Bevacizumab

Topics

• Angiogenesis Inhibitors
• Animals
• Antibodies, Monoclonal
• Antibodies, Monoclonal, Humanized
• Bevacizumab
• Colonic Neoplasms (chemistry, diagnostic imaging, pathology)
• Humans
• Immunoenzyme Techniques
• Indium Radioisotopes
• Iodine Radioisotopes
• Male
• Mice
• Mice, Inbred BALB C
• Mice, Nude
• RNA, Messenger (genetics, metabolism)
• Radionuclide Imaging
• Reverse Transcriptase Polymerase Chain Reaction
• Tissue Distribution
• Vascular Endothelial Growth Factor A (analysis)
• Xenograft Model Antitumor Assays