Micro-MR angiography of normal and intratumoral vessels in mice using dedicated intravascular MR contrast agents with high generation of polyamidoamine dendrimer core: Reference to pharmacokinetic properties of dendrimer-based MR contrast agents

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

Research output: Contribution to journalArticlepeer-review

Abstract

Pharmacokinetic characteristics of intravascular macro-molecular magnetic resonance imaging (MRI) contrast agents with polyamidoamine dendrimer cores smaller than generation-7 were previously studied in the literature. To evaluate the effects of greater hepatic uptake on the pharmacokinetics of the larger generation dendrimers, the MRI contrast agents GxD-(1B4M-Gd)2x+2 were synthesized with generation-7, -8, and -9 polyamidoamine dendrimers and 2-(p-isothiocyanatobenzyl)-6-methyl-diethylenetriaminepentaacetic acid (1B4M). Their pharmacokinetic characteristics in mice were compared with that of G6D-(1B4M-Gd)256. In biodistribution and dynamic micro-MRI studies, significantly less renal accumulation of G7D-(1B4M-Gd)512, G8D-(1B4M-Gd)1024, and G9D-(1B4M-Gd)2048 was shown compared to G6D-(1B4M-Gd)256 (P > 0.01). There was a significantly greater accumulation of G8D-(1B4M-Gd)1024 and G9D-(1B4M-Gd)2048 in the liver compared to G6D-(1B4M-Gd)256 and G7D-(1B4M-Gd)512 (P > 0.01). The highest blood retention of all dendrimer-based MRI contrast agents was exhibited by G7D(1B4M-Gd)512 (P > 0.01). The normal and intratumoral fine vessels of approximately 100 μm diameter were visualized in normal or tumor-bearing mice by high resolution three-dimension-al-micro-MR angiographs with G7D-(1B4M-Gd)512 and G8D-(1B4M-Gd)1024 with good vessel-to-soft tissue contrast. In summary, increased accumulation in the liver with concomitant decreased uptake in the kidney was caused by increased molecular sizes of the dendrimer-based MRI contrast agents.

Original languageEnglish (US)
Pages (from-to)705-713
Number of pages9
JournalJournal of Magnetic Resonance Imaging
Volume14
Issue number6
DOIs
StatePublished - 2001
Externally publishedYes

Keywords

  • Contrast media
  • Dendrimers
  • MR angiography
  • Magnetic resonance imaging
  • Pharmacokinetics

ASJC Scopus subject areas

  • Radiology Nuclear Medicine and imaging

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