Characterization of I-123-vascular endothelial growth factor-binding sitesexpressed on human tumour cells: Possible implication for tumour scintigraphy

To explore the possibility of vascular endothelial growth factor (VEGF) rec eptor scintigraphy of primary tumours and their metastases, we analysed the binding properties of (123)[labelled VEGF(165) (I-123-VEGF(165)) and I-123 -VEGF(121) to human umbilical vein endothelial cells (HUVECs), several huma n tumour cell lines (HMC-1, A43I, KU812, U937, HEP-I, HEP-G2, HEP-3B and Ra ji), a variety of primary human tumours (n = 40) and some adjacent non-neop lastic tissues as well as normal human peripheral blood cells in vitro. Two classes of high-affinity I-123-VEGF(165)-binding site were found on the ce ll surface of HUVECs. In contrast, one class of high-affinity binding sites for I-123-VEGF(165) was found on HMC-I, A43I, HEP-I, HEP-GZ, HEP-3B and U9 37 cells as well as many primary tumours. For I-123-VEGF(121), a Single cla ss of high-affinity binding site was found on certain cell lines (HUVEC, HE P-I and HMC-I) and distinct primary tumours (primary melanomas, ductal brea st cancers and ovarian carcinomas as well as meningiomas). Tumour cells exp ressed significantly higher numbers of VECF receptors compared with normal peripheral blood cells and adjacent non-neoplastic tissues. Immunohistochem ical staining revealed that the VEGF receptor Flk-I is expressed to a much higher extent within malignant tissues compared with neighbouring non-neopl astic cells. We observed significantly greater specific binding of I-123-VE GF(165) and I-123-VEGF(121) to a variety of human tumour cells/tissues comp ared with the corresponding normal tissues or normal peripheral blood cells . In comparison with I-123-VEGF(121), I-123-VEGF(121) bound to a higher num ber of different tumour cell types with a higher capacity. Thus, I-123-VEGF (165) may be a potentially useful tracer for in vivo imaging of solid rumou rs. (C) 2001 Wiley-Liss, Inc.