Radioiodinated VEGF to image tumor angiogenesis in a LS180 tumor xenograft model

IntroductionAngiogenesis is essential for tumor growth or metastasis. A method involving noninvasive detection of angiogenic activity in vivo would provide diagnostic information regarding antiangiogenic therapy targeting vascular endothelial cells as well as important insight into the role of vascular endothelial growth factor (VEGF) and its receptor (flt-1 and KDR) system in tumor biology. We evaluated radioiodinated VEGF121, which displays high binding affinity for KDR, and VEGF165, which possesses high binding affinity for flt-1 and low affinity for KDR, as angiogenesis imaging agents using the LS180 tumor xenograft model.MethodsVEGF121 and VEGF165 were labeled with 125I by the chloramine-T method. Biodistribution was observed in an LS180 human colon cancer xenograft model. Additionally, autoradiographic imaging and immunohistochemical staining of tumors were performed with 125I-VEGF121.Results125I-VEGF121 and 125I-VEGF165 exhibited strong, continuous uptake by tumors and the uterus, an organ characterized by angiogenesis. 125I-VEGF121 uptake in tumors was twofold higher than that of 125I-VEGF165 (9.12±98 and 4.79±1.08 %ID/g at 2 h, respectively). 125I-VEGF121 displayed higher tumor to nontumor (T/N) ratios in most normal organs in comparison with 125I-VEGF165. 125I-VEGF121 accumulation in tumors decreased with increasing tumor volume. Autoradiographic and immunohistochemical analyses confirmed that the difference in 125I-VEGF121 tumor accumulation correlated with degree of tumor vascularity.ConclusionRadioiodinated VEGF121 is a promising tracer for noninvasive delineation of angiogenesis in vivo.