Molecular Imaging of Arthritis in the Angiogenic Vasculature Using A123I-Vascular Endothelial Growth Factor Receptor Antibody

Abstract

Vascular endothelial growth factor (VEGF) and its receptor (VEGFR) have been implicated in the pathogenesis of rheumatoid arthritis, which is angiogenesis dependent. Antibody-based molecular imaging improves targeting, and antibody radiolabeling is useful for monitoring biological events <TEX>$in$</TEX> <TEX>$vivo$</TEX> <TEX>$via$</TEX> PET or SPECT. We investigated the potential of molecular imaging to diagnose arthritis with VEGFR-2 <TEX>$in$</TEX> <TEX>$vivo$</TEX>. The <TEX>$^{123}I$</TEX>-VEGFR-2 antibody was prepared by the iodogen tube method. The radioligand was injected into arthritic mice, and micro SPECT/CT was performed. The arthritic mice were examined by 4.7-T MRI and immunohistochemistry. The <TEX>$^{123}I$</TEX>-VEGFR-2 antibody showed high uptake in the arthritic region at 1 h postinjection on SPECT/CT but no uptake in the control animals after radioligand injection. In MR images, the arthritic tissue of the mice was correlated with regions labeled by the <TEX>$^{123}I$</TEX>-VEGFR-2 antibody. Immunohistochemical localization showed markedly increased expression of VEGFR-2 in the endothelial cells, fibroblasts, and macrophages of the arthritic mice.