Full Paper

Nanoparticle pharmacokinetic profiling in vivo using magnetic resonance imaging

  1. Anne M. Neubauer1,
  2. Hoon Sim2,
  3. Patrick M. Winter1,
  4. Shelton D. Caruthers1,3,
  5. Todd A. Williams1,
  6. J. David Robertson4,
  7. David Sept2,
  8. Gregory M. Lanza1,
  9. Samuel A. Wickline1,*

Article first published online: 24 NOV 2008

DOI: 10.1002/mrm.21795

Issue

Magnetic Resonance in Medicine

Magnetic Resonance in Medicine

Volume 60, Issue 6, pages 1353–1361, December 2008

Additional Information

How to Cite

Neubauer, A. M., Sim, H., Winter, P. M., Caruthers, S. D., Williams, T. A., Robertson, J. D., Sept, D., Lanza, G. M. and Wickline, S. A. (2008), Nanoparticle pharmacokinetic profiling in vivo using magnetic resonance imaging. Magnetic Resonance in Medicine, 60: 1353–1361. doi: 10.1002/mrm.21795

Author Information

  1. 1

    Consortium for Translational Research in Advanced Imaging and Nanomedicine, Washington University, St Louis, Missouri

  2. 2

    Department of Biomedical Engineering, Washington University, St. Louis, Missouri

  3. 3

    Philips Medical Systems, Andover, Massachusetts

  4. 4

    Analytical Chemistry Group, University of Missouri Research Reactor, Columbia, Missouri

*Biomedical Engineering, Physics, and Cellular Biology; Washington University C-TRAIN Group, Campus Box 8215 Cortex Building, Suite 101, 4320 Forest Park Avenue, St Louis, MO 63108

Publication History

  1. Issue published online: 24 NOV 2008
  2. Article first published online: 24 NOV 2008
  3. Manuscript Accepted: 28 JUL 2008
  4. Manuscript Revised: 24 JUN 2008
  5. Manuscript Received: 14 NOV 2007

Funded by

  • National Institutes of Health's Bioengineering Research Partnership. Grant Number: R01 HL073646-03
  • National Cancer Institute's Siteman Cancer Center for Nanotechnology Excellence. Grant Number: U54 CA119342-02
  • Olin Fellowship for Women

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Keywords:

  • nanoparticles;
  • αvβ3-integrin;
  • pharmacokinetic;
  • binding

Abstract

Contrast agents targeted to molecular markers of disease are currently being developed with the goal of identifying disease early and evaluating treatment effectiveness using noninvasive imaging modalities such as MRI. Pharmacokinetic profiling of the binding of targeted contrast agents, while theoretically possible with MRI, has thus far only been demonstrated with more sensitive imaging techniques. Paramagnetic liquid perfluorocarbon nanoparticles were formulated to target αvβ3-integrins associated with early atherosclerosis in cholesterol-fed rabbits to produce a measurable signal increase on magnetic resonance images after binding. In this work, we combine quantitative information of the in vivo binding of this agent over time obtained by means of MRI with blood sampling to derive pharmacokinetic parameters using simultaneous and individual fitting of the data to a three compartment model. A doubling of tissue exposure (or area under the curve) is obtained with targeted as compared to control nanoparticles, and key parameter differences are discovered that may aid in development of models for targeted drug delivery. Magn Reson Med 60:1353–1361, 2008. © 2008 Wiley-Liss, Inc.

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