Kobayashi H, Sato N, Kawamoto S, Saga T, Hiraga A, Ishimori T, Konishi J, Togashi K, Brechbiel M W
Hitachi Medical Co. Chaired Department of Diagnostic and Interventional Imaging, Kyoto University, Kyoto, Japan.
Magn Reson Med. 2001 Sep;46(3):457-64. doi: 10.1002/mrm.1214.
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 of a macromolecular MRI-CA (generation-4 PAMAM 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-dynamic-micro-MRI with G4D-(1B4M-Gd)64 was obtained with and without lysine coinjection, and the serial signal intensity (SI) change in the blood and organs was evaluated. When lysine was coinjected, urinary excretion of G4D-(1B4M-Gd)64 increased 5.4-fold compared to that without lysine, resulting in decreased renal accumulation of G4D-(1B4M-Gd)64 from 150% to 40% injected dose per gram (P < 0.001). On dynamic MRI with G4D-(1B4M-Gd)64, when lysine was coinjected, the kidney-to-blood SI ratio was significantly lower than that obtained without lysine (P < 0.001). When lysine was coinjected, the G4D-(1B4M-Gd)64 was excreted from the kidney intact.
