In vivo Magnetic Resonance Imaging of Atherosclerotic Lesions with a Newly Developed Evans Blue-DTPA-Gadolinium Contrast Medium in Apolipoprotein-E-Deficient Mice

Yasuda, Satoshi
Ikuta, Kenjiro
Uwatoku, Toyokazu
Oi, Keiji
Abe, Kohtaro
Hyodo, Fuminori
Yoshimitsu, Kengo
Sugimura, Kohtaro
Utsumi, Hideo
Katayama, Yoshiki
Shimokawa, Hiroaki

^aDepartment of Cardiovascular Medicine, Tohoku University Graduate School of Medicine, Sendai, ^bDepartment of Cardiovascular Medicine, Kyushu University Graduate School of Medical Sciences, ^cDepartment of Applied Chemistry, Faculty of Engineering, Kyushu University, ^dLaboratory of Biofunction Science, Graduate School of Pharmaceutical Sciences, Kyushu University, and ^eDepartment of Radiology, Kyushu University Hospital, Fukuoka, and ^fTechnology Agency, CREST, Tokyo, Japan

Dr. Satoshi Yasuda, Department of Cardiovascular Medicine, Tohoku University Graduate School of Medicine, 1-1 Seiryo-machi, Aoba-ku, Sendai 980-8574 (Japan), Tel. +81 22 717 7153, Fax +81 22 717 7156, E-Mail [email protected]

Received: March 27, 2007, Accepted after revision: August 11, 2007

Published online: October 16, 2007

Journal of Vascular Research 45(2):p 123-128, February 2008.

Background

Magnetic resonance imaging (MRI) contrast agents that specifically detect atherosclerotic plaque may be useful for the noninvasive detection of the plaque. We have recently developed a new contrast agent, Evans blue-DTPA-gadolinium (EB-DTPA-Gd), which selectively accumulates vascular lesions with endothelial removal. In this study, we examined whether EB-DTPA-Gd is also useful for in vivo imaging of atherosclerotic plaques.

Methods

We used male apolipoprotein-E-deficient (ApoE–/–) mice of different ages (3, 6 and 12 months old) and age-matched male wild-type mice. After a single intravenous administration of EB-DTPA-Gd (160 μM/kg body weight), MRI T₁ signal was obtained in vivo.

Results

Increased signal intensity in the aortic wall was noted within 10–20 min after intravenous injection of EB-DTPA-Gd and was maintained for 30 min. The MRI enhancement in the aorta of ApoE–/– mice was increased in accordance with age, whereas no such enhancement was noted in wild-type mice. Histological examination demonstrated that there was a topological correlation between the site of MRI enhancement and that of atherosclerotic plaque.

Conclusions

These results indicate that EB-DTPA-Gd is a useful MRI contrast medium for the in vivo detection of atherosclerotic plaques.