Imaging apolipoprotein AI in vivo.
Coronary disease risk increases inversely with high-density lipoprotein (HDL) level. The measurement of the biodistribution and clearance of HDL in vivo, however, has posed a technical challenge. This study presents an approach to the development of a lipoprotein MRI agent by linking gadolinium methanethiosulfonate (Gd[MTS-ADO3A]) to a selective cysteine mutation in position 55 of apo AI, the major protein of HDL. The contrast agent targets both liver and kidney, the sites of HDL catabolism, whereas the standard MRI contrast agent, gadolinium-diethylenetriaminepentaacetic acid-bismethylamide (GdDTPA-BMA, gadodiamide), enhances only the kidney image. Using a modified apolipoprotein AI to create an HDL contrast agent provides a new approach to investigate HDL biodistribution, metabolism and regulation in vivo.
Biochemistry and Molecular Medicine, University of California Davis, Davis, CA 95616-8635, USA.
Renuka
R
Sriram
Jens O
JO
Lagerstedt
Jitka
J
Petrlova
Haris
H
Samardzic
Ulrike
U
Kreutzer
Hongtao
H
Xie
George A
GA
Kaysen
Jean F
JF
Desreux
David
D
Thonon
Vincent
V
Jacques
Martha
M
Van Loan
John C
JC
Rutledge
Michael N
MN
Oda
John C
JC
Voss
Thomas
T
Jue
D000818:Animals; D016632:Apolipoprotein A-I / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D003287:Contrast Media / Q000737:chemistry / Q000378:metabolism; D003327:Coronary Disease / Q000378:metabolism; D005682:Gadolinium / Q000737:chemistry / Q000378:metabolism*; D006801:Humans; D007668:Kidney / Q000033:anatomy & histology / Q000378:metabolism; D008075:Lipoproteins, HDL / Q000737:chemistry / Q000378:metabolism*; D008099:Liver / Q000033:anatomy & histology / Q000378:metabolism; D008279:Magnetic Resonance Imaging / Q000379:methods*; D008297:Male; D008698:Mesylates / Q000737:chemistry / Q000378:metabolism; D051379:Mice; D008958:Models, Molecular; D017433:Protein Structure, Secondary
D016632:Apolipoprotein A-I; D003287:Contrast Media; D008075:Lipoproteins, HDL; D008698:Mesylates; C074502:methanethiosulfonate; D005682:Gadolinium
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