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. © 2001 Wiley‐Liss, Inc.