Macromolecular MRI contrast agents with small dendrimers: pharmacokinetic differences between sizes and cores

Bioconjug Chem. 2003 Mar-Apr;14(2):388-94. doi: 10.1021/bc025633c.

Abstract

Large macromolecular MRI contrast agents with albumin or dendrimer cores are useful for imaging blood vessels. However, their prolonged retention is a major limitation for clinical use. Although smaller dendrimer-based MRI contrast agents are more quickly excreted by the kidneys, they are also able to visualize vascular structures better than Gd-DTPA due to less extravasation. Additionally, unlike Gd-DTPA, they transiently accumulate in renal tubules and thus also can be used to visualize renal structural and functional damage. However, these dendrimer agents are retained in the body for a prolonged time. The purpose of this study was to obtain information from which a macromolecular dendrimer-based MRI contrast agents feasible for use in further clinical studies could be chosen. Six small dendrimer-based MRI contrast agents were synthesized, and their pharmacokinetics, whole-body retention, and dynamic MRI were evaluated in mice to determine an optimal agent in comparison to Gd-[DTPA]-dimeglumine. Diaminobutane (DAB) dendrimer-based agents cleared more rapidly from the body than polyamidoamine (PAMAM) dendrimer-based agents with the same numbers of branches. Smaller dendrimer conjugates were more rapidly excreted from the body than the larger dendrimer conjugates. Since PAMAM-G2, DAB-G3, and DAB-G2 dendrimer-based contrast agents showed relatively rapid excretion, these three conjugates might be acceptable for use in further clinical applications.

MeSH terms

  • Animals
  • Chelating Agents / chemistry
  • Chemical Phenomena
  • Chemistry, Physical
  • Contrast Media / chemical synthesis
  • Contrast Media / chemistry*
  • Contrast Media / pharmacokinetics*
  • Dendrimers
  • Female
  • Gadolinium
  • Gadolinium DTPA / chemistry
  • Magnetic Resonance Imaging*
  • Mice
  • Mice, Nude
  • Molecular Weight
  • Polyamines / chemistry
  • Quality Control
  • Tissue Distribution

Substances

  • Chelating Agents
  • Contrast Media
  • Dendrimers
  • PAMAM Starburst
  • Polyamines
  • Gadolinium
  • Gadolinium DTPA