Neuroscience 2004 Abstract
| Presentation Number: | 12.6 |
|---|---|
| Abstract Title: | Noninvasive detection of gene delivery in the brain using MRI. |
| Authors: |
Liu, C. H.*1
; Kim, Y. R.1
; Rosen, B. R.1
; Liu, P. K.1
1Radiology, Massachusetts Gen. Hosp., Charlestown, MA |
| Primary Theme and Topics |
Techniques in Neuroscience - Molecular and genetic techniques |
| Secondary Theme and Topics | Techniques in Neuroscience<br />- Staining, tracing and imaging techniques |
| Session: |
12. Molecular and Genetic Techniques and Bioinformatics Slide |
| Presentation Time: | Saturday, October 23, 2004 2:15 PM-2:30 PM |
| Location: | San Diego Convention Center - Room 2 |
| Keywords: | ANTISENSE, C-FOS, UPTAKE, BRAIN IMAGING |
The purpose of this study was to detect the uptake and distribution of oligodeoxynucleotides (ODN) delivered to the brain using high-resolution magnetic resonance imaging (MRI) in live animals. We used a phosphorothioated ODN (s-ODN) of 26-mer, which interfered the expression of Fos/AP-1 activities after stroke of rats [J. Neuroscience 19:2784; Brain Res 832:112-117]. Monocrystalline iron oxide nanoparticles (MION) were covalently bound to the s-ODN as a novel MR contrast agent. MION is a MR T2 agent, which reduces the signal intensity of its surrounding medium in the T2*-weighted MR images. We investigated two groups of animals in this study: control animals with MION only and animals with the novel conjugate, MION-s-ODN (2 ug MION in 2 ul artificial CSF per animal). MION or MION-s-ODN was delivered to the brain of C57bB6 mice (20 gm) via intracerrebroventricular route. Immediately following infusion, we observed a significant, bilateral signal reduction within the ventricular space of all animals in the T2*-weighted MR images. The MR signal from the cortex, hippocampus, and the striatum of animals infused with MION-s-ODN remained significantly reduced at 24 hours post infusion (n=10). The signal intensity in the ventricle of the control animals, however, returned to the baseline, generally within 3 hours of infusion, suggesting the wash out of MION. In experiments when s-ODN in MION-s-ODN was labeled with fluorescein isothiocyanate, we observed the presence of nuclear s-ODN in the cortex, hippocampus, the striatum and the corpus callosum (n = 4). This result showed that (1) regions of s-ODN uptake coincided with areas of signal reduction (therefore, MION retention), and (2) MION-retention appeared to be s-ODN dependent. This s-ODN-labeled contrast agent for MRI opens up a new and novel venue for non-invasive and direct molecular imaging for clinical applications.
Supported by NINDS RO1NS45845 and MGH/MIT/HMS A.A. Martinos Center for Biomedical Imaging
Sample Citation:
[Authors]. [Abstract Title]. Program No. XXX.XX. 2004 Neuroscience Meeting Planner. San Diego, CA: Society for Neuroscience, 2004. Online.
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