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The Journal of Neuroscience, August 26, 2009, 29(34):10663-10670; doi:10.1523/JNEUROSCI.2167-09.2009

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Neurobiology of Disease
DNA-Based MRI Probes for Specific Detection of Chronic Exposure to Amphetamine in Living Brains

Christina H. Liu,1,2 Jia Q. Ren,1,2 Jinsheng Yang,3 Charng-ming Liu,1,2 Joseph B. Mandeville,2 Bruce R. Rosen,2 Pradeep G. Bhide,4 Yuchio Yanagawa,5 and Philip K. Liu1,2

1Laboratory for Gene Transcript Targeting, Imaging and Repair, 2Department of Radiology, A. A. Martinos Center for Biomedical Imaging, and Departments of 3Pediatrics and 4Neurology, Massachusetts General Hospital, Charlestown, Massachusetts 02129, and 5Gunma University Graduate School of Medicine, Maebashi 371-8511, Japan

Correspondence should be addressed to Dr. Philip K. Liu, Laboratory for Gene Transcript Targeting, Imaging and Repair, Department of Radiology, Massachusetts General Hospital, 149 13th Street, Room 2301, Charlestown, MA 02129. Email: philipl{at}nmr.mgh.harvard.edu

We designed phosphorothioate-modified DNA probes linked to superparamagnetic iron oxide nanoparticles (SPION) for in vivo magnetic resonance imaging (MRI) of fosB and {Delta}fosB mRNA after amphetamine (AMPH) exposure in mice. Specificity of both the fosB and {Delta}fosB probes was verified by in vitro reverse transcriptase-PCR amplification to a single fragment of total cDNA obtained from acutely AMPH-exposed mouse brains. We confirmed time-dependent uptake and retention profiles of both probes in neurons of GAD67-green fluorescent protein knock-in mice. MRI signal of SPION-labeled fosB probe delivered via intracerebroventricular route was elevated in both acutely and chronically AMPH-exposed mice; the signal was suppressed by dopaminergic receptor antagonist pretreatment. SPION-labeled {Delta}fosB probe signal elevation occurred only in chronically AMPH-exposed mice. The in vivo target specificity of these probes permits reliable MRI visualization of AMPH-induced differential elevations of fosB and {Delta}fosB mRNA in living brains.

Received May 7, 2009; accepted June 26, 2009.

Correspondence should be addressed to Dr. Philip K. Liu, Laboratory for Gene Transcript Targeting, Imaging and Repair, Department of Radiology, Massachusetts General Hospital, 149 13th Street, Room 2301, Charlestown, MA 02129. Email: philipl{at}nmr.mgh.harvard.edu






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