Magnetic Resonance Lymphangiography with A Nano-Sized Gadolinium-Labeled Dendrimer in Small and Large Animal Models

Abstract

Imaging of the lymphatic system is critical in preoperative planning of resections of complex lymphatic malformations. However, safe, effective imaging methods with sufficient resolution to identify the lymphatics have been lacking. In this study, we demonstrate the use of gadolinium-labeled dendrimers to image the lymphatics in small and large animal models during magnetic resonance lymphangiography. Polyamidoamine G6-Gd_1B4M_N-hydroxysuccinimide was synthesized and administered intradermally in the extremities of normal mice and pigs at several doses. The lymphatics were well demonstrated in both animal models and there was rapid uptake in the deep lymphatic system, including the thoracic duct. A significant dose reduction was achieved (1 µmol Gd/kg) in the 35-kg pig compared with mice, while still producing excellent results. No toxicity was observed and only minor inflammatory changes were observed at the injection site 30 days later. We demonstrate that a low dose of a macromolecular magnetic resonance contrast agent can provide rapid imaging of the deep lymphatic system in both small and large animals. This data provides a basis to consider a similar agent in clinical trials.