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

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 3 T, 7 T and 9.4 T magnetic fields. The relaxivity-dependent albumin binding study indicated that Gd(DO3A-Lys) partially bound to albumin protein. In vitro cell viability in HK2 cell indicated low cytotoxicity of Gd(DO3A-Lys) up to 1.2 mM [Gd] concentration. In vivo toxicity studies demonstrated no toxicity of Gd(DO3A-Lys) on kidney tissues up to 0.2 mM [Gd]. While the toxicity on liver tissue was not observed at low dosage (1.0 mM [Gd]), Gd(DO3A-Lys) cause certain damage on hepatic tissue at high dosage (2.0 mM [Gd]). The DO3A-Lys has been labeled with (68)Ga radioisotope for biodistribution studies. (68)Ga(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.

• Authors: Chang-Tong Yang, Prashant Chandrasekharan, Tao He, Zihan Poh, Anandhkumar Raju, Kai-Hsiang Chuang, Edward G Robins
• Journal: Biomaterials (Biomaterials) Vol. 35 Issue 1 Pg. 327-36 (Jan 2014) ISSN: 1878-5905 [Electronic] Netherlands
• PMID: 24138829 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2013 Elsevier Ltd. All rights reserved.

Chemical References

• Contrast Media
• Heterocyclic Compounds
• Organometallic Compounds
• gadoteridol
• Gadolinium
• Lysine

Topics

• Angiography (methods)
• Animals
• Contrast Media
• Female
• Gadolinium (administration & dosage, chemistry, pharmacokinetics)
• Half-Life
• Heterocyclic Compounds (administration & dosage, chemistry, pharmacokinetics)
• Humans
• Lysine (chemistry)
• Magnetic Resonance Imaging (methods)
• Mice
• Mice, SCID
• Neoplasms (blood supply)
• Organometallic Compounds (administration & dosage, chemistry, pharmacokinetics)
• Tissue Distribution