Detecting Growing Mammary Tumors with Monoclonal Antibodies Against Vascular Endothelial Growth Factor Receptor – 3

Paivi      Karnani; Kalevi      Kairemo; Ilari      Paakkari

doi:10.2174/1874471011003010060

Abstract

Biodistribution of the monoclonal antibody (mAb 9d9f9) against the vascular endothelial growth factor receptor- 3 (VEGFR-3) is studied here in the rat. VEGFR-3 is expressed on endothelial cells of lymphatic endothelium during the tissue growth. The mAb9d9f9 is the first specific molecular marker to the endothelial cells of high venules. The specificity was detected with immunohistochemistry of tissue samples. Materials The affinity of 125I-mAb 9d9f9 was determined in HEL leukemia cells expressing the extracellular receptor and the biodistribution was detected both by external imaging and tissue sampling in the tumor model. The imaging result with subcutaneous injections was compared to the imaging after intravenous injections. Results Targeting to the induced mammary tumors in rat was detected with immunoscintigraphy of 125I-mAb. The imaging after subcutaneous administration showed lower uptake in liver, spleen, heart and stomach than the imaging after intravenous administration. The mAb 9d9f9 accumulated to the parasternal lymphatic vessels at 16 days after the subcutaneous injections. Conclusion The mAb 9d9f9 visualized the routes of lymphatic circulation probably based on binding to this transmembrane lymphatic endothelial receptor. Immunodetection of the tumors in rat was, however, possible with these antibodies targeting to the endothelial cells lining the vascular system.

Keywords: vascular endothelial growth factor receptor, lymphatic endothelium, monoclonal antibodies, lymphoscintigraphy, radioimmunodetection

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