High-relaxivity gadolinium-modified high-density lipoproteins as magnetic resonance imaging contrast agents.
There is an ongoing desire to produce high-relaxivity, Gd-based magnetic resonance imaging (MRI) contrast agents. These may allow for lower doses to be used, which is especially important in view of the current safety concerns surrounding Gd in patients. Here we report the synthesis of a high-relaxivity MRI contrast agent, by incorporating Gd-chelating lipids that coordinate two water molecules into high-density lipoprotein (q = 2 HDL). We compared the properties of q = 2 HDL with those of an analogous HDL particle labeled with Gd-chelating lipids that coordinate only one water molecule (q = 1 HDL). We found that the q = 2 HDL possessed an elevated r(1) of 41 mM(-1) s(-1) compared to 9 mM(-1) s(-1) for q = 1 HDL at 20 MHz, but the q = 2 HDL exhibited high R(2)* values at high fields, precluding imaging above 128 MHz. While carrying out this investigation we observed that enlarged, disrupted particles were formed when the synthesis was carried out above the lipid critical micelle concentration (cmc), indicating the importance of synthesis below the cmc when modifying lipoproteins in this manner. The high relaxivity of q = 2 HDL means it will be an efficacious contrast agent for future MR imaging studies.
Molecular and Translational Imaging Institute, Mount Sinai School of Medicine, One Gustave Levy Place, P.O. Box 1234, New York, New York, USA.
Karen C
KC
Briley-Saebo
Simonetta
S
Geninatti-Crich
David P
DP
Cormode
Alessandra
A
Barazza
Willem J M
WJ
Mulder
Wei
W
Chen
Giovanni B
GB
Giovenzana
Edward A
EA
Fisher
Silvio
S
Aime
Zahi A
ZA
Fayad
D000818:Animals; D002460:Cell Line; D003287:Contrast Media; D005682:Gadolinium / Q000737:chemistry*; D008075:Lipoproteins, HDL / Q000737:chemistry* / Q000378:metabolism; D008264:Macrophages / Q000378:metabolism; D008279:Magnetic Resonance Imaging / Q000379:methods*; D051379:Mice
D003287:Contrast Media; D008075:Lipoproteins, HDL; D005682:Gadolinium