Article

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

Laboratory for Gene Transcript Targeting, Imaging and Repair, Massachusetts General Hospital, Charlestown, Massachusetts 02129, USA.
The Journal of Neuroscience : The Official Journal of the Society for Neuroscience (Impact Factor: 6.75). 09/2009; 29(34):10663-70. DOI: 10.1523/JNEUROSCI.2167-09.2009
Source: PubMed

ABSTRACT 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.

Download full-text

Full-text

Available from: Philip K Liu, Aug 16, 2015
1 Follower
 · 
188 Views
  • Source
    • "Liu et. al. in a 2009 study [17] "
    [Show abstract] [Hide abstract]
    ABSTRACT: Imaging is an important part of neuroscience research, and tremendous progress has been made in recent years. However, the standard techniques of MRI, fluorescence microscopy and radiology are facing certain limitations that the advent of nanotechnology seeks to resolve. In this review a range of nanoparticles are presented and examples are given as to how the nanoparticles can im-prove existing imaging techniques or offer entirely new possibilities for imaging in neuroscience. Prime areas of usage include signal strengthening, multi-modal imaging, higher biostability and targeting possibilities. The ad-vantages of the many available functionalization groups as well as drawbacks related to challenging production and toxicology are also discussed.
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: IMPORTANCE OF THE FIELD: With the emergence of therapeutic candidates for the incurable and rapidly progressive neurodegenerative condition of amyotrophic lateral sclerosis (ALS), it will be essential to develop easily obtainable biomarkers for diagnosis, as well as monitoring, in a disease where clinical examination remains the predominant diagnostic tool. Magnetic resonance imaging (MRI) has greatly developed over the past thirty years since its initial introduction to neuroscience. With multi-modal applications, MRI is now offering exciting opportunities to develop practical biomarkers in ALS. AREAS COVERED IN THIS REVIEW: The historical application of MRI to the field of ALS, its state-of-the-art and future aspirations will be reviewed. Specifically, the significance and limitations of structural MRI to detect gross morphological tissue changes in relation to clinical presentation will be discussed. The more recent application of diffusion tensor imaging (DTI), magnetic resonance spectroscopy (MRS), functional and resting-state MRI (fMRI & R-fMRI) will be contrasted in relation to these more conventional MRI assessments. Finally, future aspirations will be sketched out in providing a more disease mechanism-based molecular MRI. WHAT THE READER WILL GAIN: This review will equip the reader with an overview of the application of MRI to ALS and illustrate its potential to develop biomarkers. This discussion is exemplified by key studies, demonstrating the strengths and limitations of each modality. The reader will gain an expert opinion on both the current and future developments of MR imaging in ALS. TAKE HOME MESSAGE: MR imaging generates potential diagnostic, prognostic and therapeutic monitoring biomarkers of ALS. The emerging fusion of structural, functional and potentially molecular imaging will improve our understanding of wider cerebral connectivity and holds the promise of biomarkers sensitive to the earliest changes.
    Expert Opinion on Medical Diagnostics 11/2010; 4(6):483-496. DOI:10.1517/17530059.2010.536836
  • [Show abstract] [Hide abstract]
    ABSTRACT: Synthesis of nanomaterials with multi-imaging modality is of great importance in clinical molecular imaging and diagnostics. This work reports novel synthetic strategy to create ultrasmall and hexagonal upconversion nanoparticles (UCNPs), β-NaGdF4: Yb3+, Er3+, and β-NaGdF4: Yb3+, Tm3+, with inherent magnetic and efficient upconversion properties. The use of new combination of lanthanide chloride and sodium TFA as the precursors for UCNPs gave the best results in terms of size (10−40 nm), crystallinity and morphology, and proved to be cost- and time-saving. Water solubilization of both NaGdF4: Yb3+, Er3+, and β-NaGdF4: Yb3+, Tm3+ UCNPs was achieved by homogeneous polymer coating using amphiphilic poly(acrylic acid) derivatives. The strong upconversion and magnetic properties were maintained after extensive polymer coating process. To see the potential of the UCNPs for biological applications, the surface of NaGdF4: Yb3+, Er3+ UCNPs were functionalized with Ni-nitrilotriacetate (NiNTA) moiety. The remarkable specificity of these NiNTA-UCNPs for the oligohistidine peptide was clearly shown by both magnetic resonance and optical imaging. Finally, the cellular uptake of these UCNPs was investigated by fluorescence microscope using spectral imaging technique.
    The Journal of Physical Chemistry C 11/2010; 114(49). DOI:10.1021/jp107725r · 4.84 Impact Factor
Show more