Abstract

Imaging of endothelial-specific markers is critically important in non-invasive detection of early signs of vascular pathologies (eg inflammation, atherosclerosis and angiogenesis). A model of adoptive human endothelial cell (HUVEC) transfer was used to test-specific imaging probes for human vascular disease consisting of cross-linked iron oxide (CLIO) nanoparticles conjugated to anti-human E-selectin (CLIO-F(ab')(2)). To perform in vivo imaging of E-selectin expression in functional blood vessels, human vascular endothelium cells (HUVECs) were implanted in athymic mice in Matrigel solution, which served as a temporary neovascularization scaffold after the solidification. The formation of HUVEC-containing vessels was established by histology and microscopy. CLIO-F(ab')(2) probes were administered via an i.v. injection following the induction of E-selectin expression by IL-1beta. High-resolution MR images were obtained before and after the administration of CLIO-F(ab')(2), which showed specific hypointensity only if treated with IL-1beta. A three-times higher CLIO-induced MR signal decrease on T2(*) images was measured in HUVEC implants in response to IL-1beta treatment. Image signal intensity did not change in control animals that: (1) harbored Matrigel alone, (2) in the absence of IL-1beta treatment or (3) in animals injected with CLIO linked to the idiotype-matched control F(ab')(2). Experiments in an adoptive transfer model demonstrated that HUVEC-containing neovessels are perfused and that IL-1beta inducible E-selectin expression in these vessels is detectable with non-invasive imaging by using targeted nanoparticles.