Characterization of (123)I-vascular endothelial growth factor-binding sites expressed on human tumour cells: possible implication for tumour scintigraphy.
To explore the possibility of vascular endothelial growth factor (VEGF) receptor scintigraphy of primary tumours and their metastases, we analysed the binding properties of (123)I-labelled VEGF(165) ((123)I-VEGF(165)) and (123)I-VEGF(121) to human umbilical vein endothelial cells (HUVECs), several human tumour cell lines (HMC-1, A431, KU812, U937, HEP-1, HEP-G2, HEP-3B and Raji), a variety of primary human tumours (n = 40) and some adjacent non-neoplastic tissues as well as normal human peripheral blood cells in vitro. Two classes of high-affinity (123)I-VEGF(165)-binding site were found on the cell surface of HUVECs. In contrast, one class of high-affinity binding sites for (123)I-VEGF(165) was found on HMC-1, A431, HEP-1, HEP-G2, HEP-3B and U937 cells as well as many primary tumours. For (123)I-VEGF(121), a single class of high-affinity binding site was found on certain cell lines (HUVEC, HEP-1 and HMC-1) and distinct primary tumours (primary melanomas, ductal breast cancers and ovarian carcinomas as well as meningiomas). Tumour cells expressed significantly higher numbers of VEGF receptors compared with normal peripheral blood cells and adjacent non-neoplastic tissues. Immunohistochemical staining revealed that the VEGF receptor Flk-1 is expressed to a much higher extent within malignant tissues compared with neighbouring non-neoplastic cells. We observed significantly greater specific binding of (123)I-VEGF(165) and (123)I-VEGF(121) to a variety of human tumour cells/tissues compared with the corresponding normal tissues or normal peripheral blood cells. In comparison with (123)I-VEGF(121), (123)I-VEGF(165) bound to a higher number of different tumour cell types with a higher capacity. Thus, (123)I-VEGF(165) may be a potentially useful tracer for in vivo imaging of solid tumours.
Department of Nuclear Medicine, University of Vienna, AKH, Ebene 3L, Waehringer Guertel 18-20, A-1090 Vienna, Austria. Shuren.li@akh-wien.ac.at
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Li
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Peck-Radosavljevic
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Koller
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Koller
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Kaserer
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Kreil
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Kapiotis
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Hamwi
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Weich
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Valent
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Angelberger
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Dudczak
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Virgolini
D000818:Animals; D001665:Binding Sites; D004195:Disease Models, Animal; D004591:Electrophoresis, Polyacrylamide Gel; D016228:Endothelial Growth Factors / Q000378:metabolism*; D004730:Endothelium, Vascular / Q000378:metabolism; D006801:Humans; D007124:Immunoenzyme Techniques; D007457:Iodine Radioisotopes; D008222:Lymphokines / Q000378:metabolism*; D051379:Mice; D008819:Mice, Nude; D009369:Neoplasms / Q000000981:diagnostic imaging / Q000378:metabolism*; D011877:Radionuclide Imaging; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors
D016228:Endothelial Growth Factors; D007457:Iodine Radioisotopes; D008222:Lymphokines; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors