High-relaxivity gadolinium-modified high-density lipoproteins as magnetic resonance imaging contrast agents.

High-relaxivity gadolinium-modified high-density lipoproteins as magnetic resonance imaging contrast agents.
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DOI:
10.1021/jp8108286
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发表时间:
2009-05-07
期刊:
The journal of physical chemistry. B
影响因子:
--
通讯作者:
Fayad ZA
Fayad ZA
中科院分区:
其他
文献类型:
--
作者:
Briley-Saebo KC;Geninatti-Crich S;Cormode DP;Barazza A;Mulder WJ;Chen W;Giovenzana GB;Fisher EA;Aime S;Fayad ZA

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There is an ongoing desire to produce high relaxivity, Gd-based 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 r1 of 41 mM−1s−1 compared to 9 mM−1s−1 for q=1 HDL at 20 MHz, but the q=2 HDL exhibited high R2* 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.
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