Recombinant high-density lipoprotein nanoparticles containing gadolinium-labeled cholesterol for morphologic and functional magnetic resonance imaging of the liver.
BACKGROUND
Natural high-density lipoproteins (HDL) possess important physiological functions to the transport of cholesterol from the peripheral tissues to the liver for metabolic degradation and excretion in the bile.


RESULTS
In this work, we took advantage of this pathway and prepared two different gadolinium (Gd)-DTPA-labeled cholesterol-containing recombinant HDL nanoparticles (Gd-chol-HDL) and Gd-(chol)(2)-HDL as liver-specific magnetic resonance imaging (MRI) contrast agents. The reconstituted HDL nanoparticles had structural similarity to native HDL, and could be taken up by HepG2 cells via interaction with HDL receptors in vitro. In vivo MRI studies in rats after intravenous injections of 10 μmol gadolinium per kg of recombinant HDL nanoparticles indicated that both nanoparticles could provide signal enhancement in the liver and related organs. However, different T(1)-weighted image details suggested that they participated in different cholesterol metabolism and excretion pathways in the liver.


CONCLUSIONS
Such information could be highly useful to differentiate functional changes as well as anatomic differences in the liver. These cholesterol-derived contrast agents and their recombinant HDL preparations may warrant further development as a new class of contrast agents for MRI of the liver and related organs.
School of Life Science and Biotechnology, Shanghai Jiao Tong University, Shanghai, People's Republic of China.
Mengjie
M
Rui
Wei
W
Guo
Qian
Q
Ding
Xiaohui
X
Wei
Jianrong
J
Xu
Yuhong
Y
Xu
D000818:Animals; D002470:Cell Survival; D002784:Cholesterol / Q000737:chemistry* / Q000493:pharmacokinetics; D003287:Contrast Media / Q000138:chemical synthesis / Q000737:chemistry* / Q000493:pharmacokinetics; D019786:Gadolinium DTPA / Q000737:chemistry* / Q000493:pharmacokinetics; D056945:Hep G2 Cells; D006801:Humans; D008075:Lipoproteins, HDL / Q000737:chemistry* / Q000493:pharmacokinetics; D008099:Liver / Q000033:anatomy & histology* / Q000378:metabolism / Q000502:physiology; D008279:Magnetic Resonance Imaging / Q000379:methods*; D008280:Magnetics; D053758:Nanoparticles / Q000737:chemistry* / Q000648:ultrastructure; D051381:Rats; D017207:Rats, Sprague-Dawley; D011994:Recombinant Proteins / Q000737:chemistry / Q000493:pharmacokinetics; D014018:Tissue Distribution
D003287:Contrast Media; D008075:Lipoproteins, HDL; D011994:Recombinant Proteins; D002784:Cholesterol; D019786:Gadolinium DTPA