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

Hisataka Kobayashi, Noriko Sato, Satomi Kawamoto, Tsuneo Saga, Akira Hiraga, Takayoshi Ishimori, Junji Konishi, Kaori Togashi, Martin W. Brechbiel

Research output: Contribution to journalArticlepeer-review

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 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.

Original languageEnglish (US)
Pages (from-to)457-464
Number of pages8
JournalMagnetic resonance in medicine
Volume46
Issue number3
DOIs
StatePublished - 2001
Externally publishedYes

Keywords

  • Angiography
  • Contrast media
  • Lysine
  • Magnetic resonance imaging
  • Renal excretion

ASJC Scopus subject areas

  • Radiology Nuclear Medicine and imaging

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