Novel intravascular macromolecular MRI contrast agent with generation-4 polyamidoamine dendrimer core: Accelerated renal excretion with coinjection of lysine
✍ Scribed by Hisataka Kobayashi; Noriko Sato; Satomi Kawamoto; Tsuneo Saga; Akira Hiraga; Takayoshi Ishimori; Junji Konishi; Kaori Togashi; Martin W. Brechbiel
- Publisher
- John Wiley and Sons
- Year
- 2001
- Tongue
- English
- Weight
- 487 KB
- Volume
- 46
- Category
- Article
- ISSN
- 0740-3194
- DOI
- 10.1002/mrm.1214
No coin nor oath required. For personal study only.
✦ Synopsis
Abstract
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. Magn Reson Med 46:457–464, 2001. © 2001 Wiley‐Liss, Inc.