Improving T1 and T2 magnetic resonance imaging contrast agents through the conjugation of an esteramide dendrimer to high-water-coordination Gd(III) hydroxypyridinone complexes

Piper J. Klemm, William C. Floyd, Danil E. Smiles, Jean Frechet, Kenneth N. Raymond*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

31 Scopus citations

Abstract

Commercial gadolinium magnetic resonance imaging (MRI) contrast agents are limited by low relaxivity (r1) and coordination to only a single water molecule (q=1). Consequently, gram quantities of these agents must be injected to obtain sufficient diagnostic contrast. In this study, MRI contrast agents for T1 and T2 relaxivity were synthesized using hydroxypyridinone and terephthalamide chelators with mesityl and 1,4,7-triazacyclononane capping moieties. When covalently conjugated to a highly biocompatible esteramide dendrimer, T2 relaxation rates up to 52m m -1s -1 and T1 relaxation rates up to 31m m -1s -1 per gadolinium were observed under clinically relevant conditions. These values are believed to be brought about by using a dendritic macromolecule to decrease the molecular tumbling time of the small molecule complexes. These agents also show high aqueous solubility and low toxicity in vitro. In this study we report six new compounds: three discrete complexes and three dendrimer conjugates.

Original languageEnglish (US)
Pages (from-to)95-99
Number of pages5
JournalContrast Media and Molecular Imaging
Volume7
Issue number1
DOIs
StatePublished - Jan 1 2012

Keywords

  • 1,4,7-triazacyclononane (TACN)
  • Dendrimer
  • Drug delivery
  • Esteramide (EA) dendrimer
  • Gadolinium
  • Hydroxypyridinone (HOPO)
  • MRI contrast agent
  • Relaxivity
  • Terephthalamide (TAM)

ASJC Scopus subject areas

  • Radiology Nuclear Medicine and imaging
  • Medicine(all)

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