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

Yoshimoto, Mitsuyoshi; Kinuya, Seigo; Kawashima, Atsuhiro; Nishii, Ryuichi; Yokoyama, Kunihiko; Kawai, Keiichi

doi:10.1016/j.nucmedbio.2006.08.006

« Previous Next »Nuclear Medicine and Biology
Volume 33, Issue 8 , Pages 963-969, November 2006

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

Mitsuyoshi Yoshimoto
- Division of Health Sciences, Graduate School of Medical Science, Kanazawa University, Ishikawa 920-0942, Japan
- Corresponding author. Tel.: +81 76 265 2539; fax: +81 76 234 4366.
Seigo Kinuya
- Department of Biotracer Medicine, Graduate School of Medical Science, Kanazawa University, Ishikawa 920-8640, Japan
Atsuhiro Kawashima
- Kanazawa Medical Center, Ishikawa 920-8650, Japan
Ryuichi Nishii
- Department of Radiology, Fujimoto Hayasuzu Hospital, Miyazaki 885-0055, Japan
- Biomedical Imaging Research Center, University of Fukui, Fukui 910-1193, Japan
Kunihiko Yokoyama
- Department of Biotracer Medicine, Graduate School of Medical Science, Kanazawa University, Ishikawa 920-8640, Japan
Keiichi Kawai
- Division of Health Sciences, Graduate School of Medical Science, Kanazawa University, Ishikawa 920-0942, Japan
- Biomedical Imaging Research Center, University of Fukui, Fukui 910-1193, Japan

Received 28 April 2006; received in revised form 9 August 2006; accepted 10 August 2006. published online 06 October 2006.

Abstract

Introduction

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 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.

Methods

VEGF₁₂₁ 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.

Results

¹²⁵I-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.