Radioiodinated VEGF to image tumor angiogenesis in a LS180 tumor xenograft model.
BACKGROUND
Angiogenesis 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 VEGF(121), which displays high binding affinity for KDR, and VEGF(165), which possesses high binding affinity for flt-1 and low affinity for KDR, as angiogenesis imaging agents using the LS180 tumor xenograft model.


METHODS
VEGF(121) and VEGF(165) were labeled with (125)I 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 (125)I-VEGF(121).


RESULTS
(125)I-VEGF(121) and (125)I-VEGF(165) exhibited strong, continuous uptake by tumors and the uterus, an organ characterized by angiogenesis. (125)I-VEGF(121) uptake in tumors was twofold higher than that of (125)I-VEGF(165) (9.12+/-98 and 4.79+/-1.08 %ID/g at 2 h, respectively). (125)I-VEGF(121) displayed higher tumor to nontumor (T/N) ratios in most normal organs in comparison with (125)I-VEGF(165). (125)I-VEGF(121) accumulation in tumors decreased with increasing tumor volume. Autoradiographic and immunohistochemical analyses confirmed that the difference in (125)I-VEGF(121) tumor accumulation correlated with degree of tumor vascularity.


CONCLUSIONS
Radioiodinated VEGF(121) is a promising tracer for noninvasive delineation of angiogenesis in vivo.
Yoshimoto
Mitsuyoshi
M
Division of Health Sciences, Graduate School of Medical Science, Kanazawa University, Ishikawa 920-0942, Japan. myoshi@mhs.mp.kanazawa-u.ac.jp <myoshi@mhs.mp.kanazawa-u.ac.jp>
Kinuya
Seigo
S
Kawashima
Atsuhiro
A
Nishii
Ryuichi
R
Yokoyama
Kunihiko
K
Kawai
Keiichi
K
D043168:Angiostatins / Q000378:metabolism; D000818:Animals; D001345:Autoradiography; D045744:Cell Line, Tumor; D043169:Endostatins / Q000378:metabolism; D005260:Female; D006801:Humans; D007457:Iodine Radioisotopes; D051379:Mice; D008807:Mice, Inbred BALB C; D009368:Neoplasm Transplantation; D009374:Neoplasms, Experimental / Q000098:blood supply* / Q000473:pathology; D009389:Neovascularization, Pathologic / Q000000981:diagnostic imaging*; D011877:Radionuclide Imaging; D019275:Radiopharmaceuticals; D014018:Tissue Distribution; D014183:Transplantation, Heterologous; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism*; D040281:Vascular Endothelial Growth Factor Receptor-1 / Q000378:metabolism
D043169:Endostatins; D007457:Iodine Radioisotopes; D019275:Radiopharmaceuticals; D042461:Vascular Endothelial Growth Factor A; D043168:Angiostatins; C501163:Flt1 protein, mouse; D040281:Vascular Endothelial Growth Factor Receptor-1