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A method for the making and utility of gadolinium-labeled albumin microbubbles
Authors:Anderson Daniel R  Duryee Michael J  Garvin Robert P  Boska Michael D  Thiele Geoffrey M  Klassen Lynell W
Institution:
  • a Experimental Immunology, Research in Cardiovascular Disease Laboratory at the University of Nebraska Medical Center, Division of Cardiology, Department of Internal Medicine, 982265 Nebraska Medical Center, Omaha, NE 68198-2265, USA
  • b Experimental Immunology, Research in Autoimmune Disease Laboratory at the Omaha VA Medical Center, Research Services 151, Omaha, NE 68124, USA
  • c Experimental Immunology, Research in Rheumatologic Disease Laboratory at the University of Nebraska Medical Center, Division of Rheumatology, Department of Internal Medicine, 983025 Nebraska Medical Center, Omaha, NE 68198-3025, USA
  • d Bioimaging Core Laboratory at the University of Nebraska Medical Center, Department of Radiology, 981045 Nebraska Medical Center, Omaha, NE 68198-1045, USA
  • e University of Nebraska Medical Center, Department of Pathology and Microbiology, 986495 Nebraska Medical Center, Omaha, NE 68198-6495, USA
  • Abstract:

    Objective

    Perfluorocarbon-exposed sonicated dextrose albumin microbubbles (PESDA) binds scavenger receptors and can be noninvasively imaged. To enhance imaging, gadolinium (Gd)-labeled PESDA was developed and tested in a model of vascular inflammation by magnetic resonance imaging (MRI).

    Methods and Results

    Purified human serum albumin (HSA) (5%) was labeled with Gd via the covalent binding of diethylenetriaminepentacetic acid. Abdominal aortic tissues in Sprague-Dawley rats (n=5 per group) were analyzed by 7-T MRI and scanning electron microscopy to evaluate PESDA binding. Labeling-purified 5% human albumin resulted in an average of 16.1 Gd atoms per albumin molecule as determined by atomic absorption. Forty-eight hours after balloon angioplasty, aortic tissue was enhanced with Gd-PESDA as compared to control tissue. 7-T MRI of explanted tissues was sensitive to the detection of retained PESDA. Enhancement of aortic tissue in vivo was present albeit to a lesser extent than explanted tissue from the same animals.

    Conclusions

    HSA was successfully labeled, and an albumin-based microbubble with Gd was synthesized. This contrast agent, Gd-PESDA, may serve as an additional agent for the MRI evaluation of innate inflammation and used to noninvasively image early vascular pathophysiologic processes.

    Condensed Abstract

    In this study, Gd-PESDA microbubbles and were synthesized and shown to detect the binding of these microbubbles using MRI in injured aortic tissue. The method for synthesizing Gd-PESDA is detailed, and the proposed utility of this new contrast agent is discussed.
    Keywords:Gadolinium  Magnetic Resonance Imaging  MRI  Perfluorocarbon exposed sonicated dextrose albumin  PESDA  Vascular inflammation  Scavenger receptors  Atherosclerosis
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