Novel intravascular macromolecular MRI contrast agent with generation-4 polyamidoamine dendrimer core: Accelerated renal excretion with coinjection of lysine

One of the major limitations to macromolecular MRI contrast agents (MRI-CAs ) is their slow clearance and associated decreased excretion of gadolinium (Gd(III)). The effect of coinjecting lysine to accelerate renal excretion o f a macromolecular MRI-CA (generation-4 PAMAM (TM) dendrimer (G4D-(1B4M-Gd) (64))) was investigated. The biodistribution and urine and fecal excretion in athymic mice was evaluated with and without lysine coinjection. 3D-dynam ic-micro-MRI with G4D-(1B4M-Gd)(64) was obtained with and without lysine co injection, and the serial signal intensity (SI) change in the blood and org ans was evaluated. When lysine was coinjected, urinary excretion of G4D-(1B 4M-Gd)(64) increased 5.4-fold compared to that without lysine, resulting in decreased renal accumulation of G4D(iB4M-Gd)(64) from 150% to 40% injected dose per gram (P < 0.001). On dynamic MRI with G4D-(iB4M-Gd)(64), when lys ine was coinjected, the kidney-to-blood SI ratio was significantly lower th an that obtained without lysine (P < 0.001). When lysine was coinjected, th e G4D-(iB4M-Gd)(64) was excreted from the kidney intact.