An intravascular MRI contrast agent based on Gd(DO3A-Lys) for tumor angiography

Chang Tong Yang, Prashant Chandrasekharan, Tao He, Zihan Poh, Anandhkumar Raju, Kai Hsiang Chuang, Edward G. Robins

Research output: Contribution to journalArticlepeer-review

17 Citations (Scopus)

Abstract

An intravascular MRI contrast agent Gd(DO3A-Lys), Gadolinium(III) (2,2',2″-(10-(3-(5-benzamido-6-methoxy-6-oxohexylamino)-3-oxopropyl)-1,4,7,10-tetraazacyclododecane-1,4,7-triyl)triacetate), has been studied for tumor angiography based on its high relaxivity and long blood half-life. The preparation procedures of the contrast agent have been modified in order to achieve higher yield and improve the synthetic reproducibility. High relaxivity of Gd(DO3A-Lys) has been confirmed by measurements at 3T, 7T and 9.4T magnetic fields. The relaxivity-dependent albumin binding study indicated that Gd(DO3A-Lys) partially bound to albumin protein. Invitro cell viability in HK2 cell indicated low cytotoxicity of Gd(DO3A-Lys) up to 1.2mm [Gd] concentration. Invivo toxicity studies demonstrated no toxicity of Gd(DO3A-Lys) on kidney tissues up to 0.2mm [Gd]. While the toxicity on liver tissue was not observed at low dosage (1.0mm [Gd]), Gd(DO3A-Lys) cause certain damage on hepatic tissue at high dosage (2.0mm [Gd]). The DO3A-Lys has been labeled with 68Ga radioisotope for biodistribution studies. 68Ga(DO3A-Lys) has high uptake in both HT1080 and U87MG xenograft tumors, and has high accumulation in blood. Contrast-enhanced MR angiography (CE-MRA) in mice bearing U87MG xenograft tumor demonstrated that Gd(DO3A-Lys) could enhance vascular microenvironment around the tumor, and displays promising characteristics of an MRI contrast agent for tumor angiography.

Original languageEnglish
Pages (from-to)327-336
Number of pages10
JournalBiomaterials
Volume35
Issue number1
DOIs
Publication statusPublished or Issued - 2014
Externally publishedYes

Keywords

  • Contrast agent
  • Gadolinium chelate
  • Magnetic resonance imaging (MRI)
  • Molecular imaging
  • Tumor angiography

ASJC Scopus subject areas

  • Bioengineering
  • Ceramics and Composites
  • Biophysics
  • Biomaterials
  • Mechanics of Materials

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