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 journalArticle

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

Fingerprint

Dendrimers
Contrast Media
Lysine
Kidney
PAMAM-G4
Renal Elimination
Gadolinium
Nude Mice
Urine

Keywords

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

ASJC Scopus subject areas

  • Radiology Nuclear Medicine and imaging
  • Radiological and Ultrasound Technology

Cite this

Novel intravascular macromolecular MRI contrast agent with generation-4 polyamidoamine dendrimer core : Accelerated renal excretion with coinjection of lysine. / Kobayashi, Hisataka; Sato, Noriko; Kawamoto, Satomi; Saga, Tsuneo; Hiraga, Akira; Ishimori, Takayoshi; Konishi, Junji; Togashi, Kaori; Brechbiel, Martin W.

In: Magnetic Resonance in Medicine, Vol. 46, No. 3, 2001, p. 457-464.

Research output: Contribution to journalArticle

Kobayashi, Hisataka ; Sato, Noriko ; Kawamoto, Satomi ; Saga, Tsuneo ; Hiraga, Akira ; Ishimori, Takayoshi ; Konishi, Junji ; Togashi, Kaori ; Brechbiel, Martin W. / Novel intravascular macromolecular MRI contrast agent with generation-4 polyamidoamine dendrimer core : Accelerated renal excretion with coinjection of lysine. In: Magnetic Resonance in Medicine. 2001 ; Vol. 46, No. 3. pp. 457-464.
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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.",
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