TY - JOUR
T1 - Novel intravascular macromolecular MRI contrast agent with generation-4 polyamidoamine dendrimer core
T2 - Accelerated renal excretion with coinjection of lysine
AU - Kobayashi, Hisataka
AU - Sato, Noriko
AU - Kawamoto, Satomi
AU - Saga, Tsuneo
AU - Hiraga, Akira
AU - Ishimori, Takayoshi
AU - Konishi, Junji
AU - Togashi, Kaori
AU - Brechbiel, Martin W.
PY - 2001
Y1 - 2001
N2 - 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 PAMAMTM™ 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.
AB - 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 PAMAMTM™ 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.
KW - Angiography
KW - Contrast media
KW - Lysine
KW - Magnetic resonance imaging
KW - Renal excretion
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U2 - 10.1002/mrm.1214
DO - 10.1002/mrm.1214
M3 - Article
C2 - 11550236
AN - SCOPUS:0034846014
SN - 0740-3194
VL - 46
SP - 457
EP - 464
JO - Magnetic resonance in medicine
JF - Magnetic resonance in medicine
IS - 3
ER -