Gd3+-1,4,7,10-Tetraazacyclododecane-1,4,7-triacetic-2-hydroxypropyl-β-cyclodextrin/Pluronic Polyrotaxane as a Long Circulating High Relaxivity MRI Contrast Agent

ACS Appl Mater Interfaces. 2015 Oct 14;7(40):22272-6. doi: 10.1021/acsami.5b05393. Epub 2015 Sep 29.

Abstract

A multivalent magnetic resonance imaging agent based on a 2-hydroxypropyl-β-cyclodextrin (HPCD):Pluronic F127 polyrotaxane carrier has been synthesized, and its blood pool contrast properties have been characterized. This Gd3+-DO3A-HPCD/Pluronic polyrotaxane construct is shown to circulate for more than 30 min and provide >100-fold vascular enhancement relative to the monomeric Gd3+-DO3A-HPCD control that is rapidly cleared via the kidney. The high r1 relaxivity at 37 °C (23.83 mM(-1) s(-1) at 1.5 T; 34.08 mM(-1) s(-1) at 0.5 T), extended blood circulation, well-known pharmacology of the polyrotaxane precursors, and absence of acute toxicity make it a highly attractive blood pool contrast agent candidate.

Keywords: 2-hydroxypropyl-β-cyclodextrin; Gd3+-DO3A; Pluronic; blood pool MR agent; long circulation; magnetic resonance contrast agent; polyrotaxane.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • 2-Hydroxypropyl-beta-cyclodextrin
  • Animals
  • Contrast Media / chemistry*
  • Contrast Media / pharmacokinetics
  • Coordination Complexes / chemical synthesis
  • Coordination Complexes / chemistry
  • Cyclodextrins / chemistry*
  • Gadolinium / chemistry*
  • Heterocyclic Compounds, 1-Ring / chemistry
  • Magnetic Resonance Imaging
  • Mice
  • Mice, Inbred BALB C
  • Poloxamer / chemistry*
  • Rotaxanes / chemistry*
  • Tissue Distribution
  • beta-Cyclodextrins / chemistry*

Substances

  • 1,4,7,10-tetraazacyclododecane-1,4,7-triacetic acid
  • Contrast Media
  • Coordination Complexes
  • Cyclodextrins
  • Heterocyclic Compounds, 1-Ring
  • Rotaxanes
  • beta-Cyclodextrins
  • polyrotaxane
  • Poloxamer
  • 2-Hydroxypropyl-beta-cyclodextrin
  • Gadolinium