Anti-VEGFR2-conjugated PLGA microspheres as an x-ray phase contrast agent for assessing the VEGFR2 expression

The primary goal of this study was to evaluate the feasibility of using anti-vascular endothelial growth factor receptor 2 (VEGFR2)-conjugated poly(lactic-co-glycolic acid) (PLGA) microspheres as an x-ray phase contrast agent to assess the VEGFR2 expression in cell cultures. The cell lines, mouse LLC (Lewis lung carcinoma) and HUVEC (human umbilical vein endothelial cell), were selected for cell adhesion studies. The bound PLGA microspheres were found to better adhere to LLC cells or HUVECs than unbound ones. Absorption and phase contrast images of PLGA microspheres were acquired and compared in vitro. Phase contrast imaging (PCI) greatly improves the detection of the microspheres as compared to absorption contrast imaging. The cells incubated with PLGA microspheres were imaged by PCI, which provided clear 3D visualization of the beads, indicating the feasibility of using PLGA microspheres as a contrast agent for phase contrast CT. In addition, the microspheres could be clearly distinguished from the wall of the vessel on phase contrast CT images. Therefore, the approach holds promise for assessing the VEGFR2 expression on endothelial cells of tumor-associated vessels. We conclude that PLGA microsphere-based PCI of the VEGFR2 expression might be a novel, promising biomarker for future studies of tumor angiogenesis.