Comparison of dendrimer-based macromolecular contrast agents for dynamic micro-magnetic resonance lymphangiography

Few methods are currently available to visualize the entire lymphatic system. A method known as micro-magnetic resonance lymphangiography (MRL), which employs a dendrimer-based MRI contrast agent (PAMAM-G8) and a clinical-grade 1.5T MRI instrument, was recently developed for use in mice. In the present study, three dendrimer-based MRI contrast agents (PAMAM-G8, DAB-G5, and PAMAM-G4) with different pharmacokinetic characteristics were compared to determine the best reagent to visualize the lymphatic system under physiological or pathological conditions. In addition, two established MRI contrast agents (Gadomer-17 and Gd-[DTPA]-dimeglumine (Magnevist)) were used as control agents. In experiments with mice, most of the deep lymphatic system was visualized by micro-MRL with all agents except Gd-[DTPA]-dimeglumine. PAMAM-G8 was best for visualizing lymphatic vessels, whereas DAB-G5 was better for visualizing lymph nodes. PAMAM-G4 was intermediate in character between PAMAM-G8 and DAB-G5, except in exhibiting a low background signal (especially in the liver). The lymphatic system was not clearly visualized with Gd-[DTPA]-dimeglumine; however, the lymph nodes were visualized with Gadomer-17, although not as well as with dendrimer-based agents. In conclusion, DAB-G5 and PAMAM-G4 can be used to identify lymph nodes and lymphatic vessels, respectively. Their rapid excretion makes these compounds potentially attractive for human use.