Imaging apolipoprotein AI in vivo - PubMed (original) (raw)

doi: 10.1002/nbm.1650. Epub 2011 Jan 24.

Jens O Lagerstedt, Jitka Petrlova, Haris Samardzic, Ulrike Kreutzer, Hongtao Xie, George A Kaysen, Jean F Desreux, David Thonon, Vincent Jacques, Martha Van Loan, John C Rutledge, Michael N Oda, John C Voss, Thomas Jue

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Imaging apolipoprotein AI in vivo

Renuka Sriram et al. NMR Biomed. 2011 Aug.

Abstract

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.

Copyright © 2011 John Wiley & Sons, Ltd.

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Figures

Figure 1

Figure 1

Molecular structure of gadolinium methanethiosulfonate (Gd[MTS-ADO3A]) and variants of apolipoprotein AI (apo AI). The structure of Gd[MTS-ADO3A] is shown on the left with the thioester linker. On the right is the ribbon diagram of the protein apo AI with cysteine (Cys) replacing serine at position 55 or glutamine at position 76.

Figure 2

Figure 2

Sagittal views of mouse liver and kidney: (A) during control period (prior to the injection of contrast agent); (B) 5 min after infusion of gadodiamide; (C) during control period; (D) 5 min after infusion of Gd[MTS-ADO3A]apo AI-S55C.

Figure 3

Figure 3

Bar graphs of image intensity in kidney medulla in the control period (prior to the injection of contrast agent) (□) and 5 min (▦), 10 min (▨) and 30 min (▥) after the infusion of gadodiamide and Gd[MTS-ADO3A]apo AI-S55C.

Figure 4

Figure 4

Bar graphs of image intensity in liver in the control period (prior to the injection of contrast agent) (□) and 5 min (▦), 10 min (▨) and 30 min (▥) after the infusion of gadodiamide and Gd[MTS-ADO3A]apo AI-S55C.

Figure 5

Figure 5

Western blot of extracts from the control period (prior to the injection of contrast agent) and from liver and kidney infused with gadodiamide (lanes 03L and 03K, respectively) and Gd[MTS-ADO3A]apo AI-S55C (lanes A5L and A5K, respectively). The 25- and 75-kDa bands in lanes A5L and A5K correspond to monomeric and oligomeric apolipoprotein AI.

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