Gd-based protein cage nanoparticles provide enhanced r1 relaxivity and detect experimental atherosclerosis
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POSTER PRESENTATION
Open Access
Gd-based protein cage nanoparticles provide enhanced r1 relaxivity and detect experimental atherosclerosis Lars O Liepold1, Masaki Uchida1*, Md Joynald Abedin1, Shefah Qazi1, Hisanori Kosuge2, Toshiro Kitagawa2, Michael V McConnell2, Trevor Douglas1 From 2011 SCMR/Euro CMR Joint Scientific Sessions Nice, France. 3-6 February 2011 Objective Develop a highly sensitive T1 contrast agent based on chemically attaching a multitude of chelated Gd molecules constrained within a protein cage structure.
exterior diameter and a 9nm interior cavity, as a platform to anchor Gd-DTPA.
Methods 1) Material development and evaluation
Background A T1 nanoparticle contrast agent showing high r1 relaxivity is desired to provide more sensitive molecular/ cellular imaging with reduced Gd dose, and may have more clinical utility than T2* (e.g., iron-based) approaches. Tethering multiple Gd-chelates to a supramolecular platform is a promising strategy to increase r1 relaxivity, as rotational correlation time of the Gd ions can become significantly larger which is highly favorable for efficient r1 relaxivity. Here we utilize a small heat shock protein cage (Hsp) with a 12nm
Hsp was purified from an E. coli expression system. An azide-alkyne based click reaction is cycled to produce a branched polymer network in the interior of the protein cage (Fig 1). The polymer results in a stable network containing Gd-DTPA, as the azide-containing monomer has the Gd chelate attached prior to polymer generation. 2) In vivo imaging of vascular inflammation
FVB mice underwent left carotid ligation after 4 weeks of high-fat diet and diabetes induction by streptozotocin. Two weeks later, Hsp-Gd or Magnevist (Gd-DTPA)
Figure 1 Illustration of Hsp-brach polymer with Gd.
1 Montana State University, Bozeman, MT, USA Full list of author information is available at the end of the article
© 2011 Liepold et al; licensee BioMed Central Ltd. This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Liepold et al. Journal of Cardiovascular Magnetic Resonance 2011, 13(Suppl 1):P370 http://jcmr-online.com/content/13/S1/P370
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Results In vitro analysis of Hsp-Gd showed about 160 GdDTPA molecules per cage. At 0.73T, the ionic (per Gd) r1 value is 25mM -1 sec -1 and the particle r1 value is 4,200mM-1sec-1 (Fig 2). At 3T, the ionic and particle r1 values are 9.7 mM-1sec-1 and 1600 mM-1sec-1, respectively. The ionic r1 value is nearly 3 times higher than that of Magnevist. The macrophage-rich left carotid lesion, but not the non-ligated right carotid, was clearly detected on T1-weighted MR imaging 4h after injection of Hsp-Gd, whereas the same lesion was hardly detected after Magnevist injection (Fig. 3).
Figure 2 Graph of r1 measurement at varying field.
was intravenously injected at a dose of 20µmol Gd/kg
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