Development of intravascular contrast agents for MRI using gadolinium chelates

Krisada Kittigowittana, Chang Tong Yang, Wai Ching Cheah, Kai Hsiang Chuang, Chew Yuan Tuang, Young Tae Chang, Xavier Golay, Roderick W. Bates

Research output: Contribution to journalArticlepeer-review

Abstract

Two MRI contrast agents (CAs) composed of Gd-DO3A conjugated to amino acid building blocks derived from glutamic acid (CA1) and lysine (CA2) have been synthesized by using novel alkyne and propionate linkers, and subsequently characterized. Invitro cell viability assays showed insignificant cytotoxicity of both CAs at low concentrations up to 0.2mM. The longitudinal relaxivities (r1) of CA1 and CA2 measured at 9.4T are 6.4 and 5.4mM-1s-1 in H2O at 25°C, respectively. Both r1 values are higher than those of CAs in clinical use: Gd-DTPA (Magnevist, Bayer Schering, Germany) and Gd-DOTA (Dotarem, Guerbet, France). Invivo imaging in Wistar rats demonstrated considerable signal enhancement (∼50%) in the brain artery by CA2, but lower signal enhancement (∼30%) by CA1. In contrast to Dotarem, which showed a similar signal enhancement as CA2, the enhancement by CA2 remained high (∼30%), even at 52min post-injection. This demonstrates that CA2 has a much longer blood half-life (68.1min), which could be advantageous for angiography and tissue targeting. Image this! Herein we describe the preparation and characterization of GdIII chelates CA1 and CA2, which use novel linkers to connect the cyclen to the amino acid residue. Invivo imaging in Wistar rats demonstrated considerable signal enhancement and long blood retention time in the brain artery for CA2.

Original languageEnglish (US)
Pages (from-to)781-787
Number of pages7
JournalChemMedChem
Volume6
Issue number5
DOIs
StatePublished - May 2 2011

Keywords

  • Amino acids
  • Contrast agents
  • Gadolinium
  • Intravascular
  • Magnetic resonance imaging

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Medicine
  • Pharmacology
  • Drug Discovery
  • Pharmacology, Toxicology and Pharmaceutics(all)
  • Organic Chemistry

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