Louie, A.Y. et al. In vivo visualization of gene expression using magnetic resonance imaging. Nat. Biotechnol. 18, 321−325

Division of Biology Beckman Institute, California Institute of Technology, Pasadena, CA 91125, USA.
Nature Biotechnology (Impact Factor: 41.51). 04/2000; 18(3):321-5. DOI: 10.1038/73780
Source: PubMed


High-resolution in vivo imaging of gene expression is not possible in opaque animals by existing techniques. Here we present a new approach for obtaining such images by magnetic resonance imaging (MRI) using an MRI contrast agent that can indicate reporter gene expression in living animals. We have prepared MRI contrast agents in which the access of water to the first coordination sphere of a chelated paramagnetic ion is blocked with a substrate that can be removed by enzymatic cleavage. Following cleavage, the paramagnetic ion can interact directly with water protons to increase the MR signal. Here, we report an agent where galactopyranose is the blocking group. This group renders the MRI contrast agent sensitive to expression of the commonly used marker gene, beta-galactosidase. To cellular resolution, regions of higher intensity in the MR image correlate with regions expressing marker enzyme. These results offer the promise of in vivo mapping of gene expression in transgenic animals and validate a general approach for constructing a family of MRI contrast agents that respond to biological activity.

Download full-text


Available from: Rex A Moats
  • Source
    • "Another important challenge for MR contrast agent design is to generate bioactivated and theranostic agents that can be used in complex, physiological conditions. Bioactivated MR agents can be utilized to report enzymatic activities [43, 44], gene expression (e.g., β-galactosidase [45], β-glucoronidase, caspases [46], metalloproteinases (MMPs) (e.g., [47, 48])) as well as signal transduction and intracellular messengers such as Ca2+ [49] and Zn2+ (e.g., [50, 51]). It was observed that currently all MR-based molecular imaging probes are for preclinical and investigational use only. "
    [Show abstract] [Hide abstract]
    ABSTRACT: A workshop on "Clinical Translation of Molecular Imaging Probes and Technology" was held August 2, 2013 in Bethesda, Maryland, organized and supported by the National Institute of Biomedical Imaging and Bioengineering (NIBIB). This workshop brought together researchers, clinicians, representatives from pharmaceutical companies, molecular probe developers, and regulatory science experts. Attendees met to talk over current challenges in the discovery, validation, and translation of molecular imaging (MI) probes for key clinical applications. Participants also discussed potential strategies to address these challenges. The workshop consisted of 4 sessions, with 14 presentations and 2 panel discussions. Topics of discussion included (1) challenges and opportunities for clinical research and patient care, (2) advances in molecular probe design, (3) current approaches used by industry and pharmaceutical companies, and (4) clinical translation of MI probes. In the presentations and discussions, there were general agreement that while the barriers for validation and translation of MI probes remain high, there are pressing clinical needs and development opportunities for targets in cardiovascular, cancer, endocrine, neurological, and inflammatory diseases. The strengths of different imaging modalities, and the synergy of multimodality imaging, were highlighted. Participants also underscored the continuing need for close interactions and collaborations between academic and industrial partners, and federal agencies in the imaging probe development process.
    Full-text · Article · May 2014 · Molecular imaging and biology: MIB: the official publication of the Academy of Molecular Imaging
  • Source
    • "Moreover, several nanoparticles such as gold nanoparticles [13, 14] and polymer-coated bismuth sulfide nanoparticles [15] have emerged as novel CT contrast agents for cancer detection. Similarly, some novel genetically encoded MRI contrast agents and advanced sequence technologies have been used to detect gene expression [16–19]. Finally, due to the advantages of cost, convenience (for CT), and safety (for MRI), both CT and MRI will be appropriate imaging techniques for imaging-omics integration. "
    [Show abstract] [Hide abstract]
    ABSTRACT: During the past decade, medical imaging has made the transition from anatomical imaging to functional and even molecular imaging. Such transition provides a great opportunity to begin the integration of imaging data and various levels of biological data. In particular, the integration of imaging data and multiomics data such as genomics, metabolomics, proteomics, and pharmacogenomics may open new avenues for predictive, preventive, and personalized medicine. However, to promote imaging-omics integration, the practical challenge of imaging techniques should be addressed. In this paper, we describe key challenges in two imaging techniques: computed tomography (CT) and magnetic resonance imaging (MRI) and then review existing technological advancements. Despite the fact that CT and MRI have different principles of image formation, both imaging techniques can provide high-resolution anatomical images while playing a more and more important role in providing molecular information. Such imaging techniques that enable single modality to image both the detailed anatomy and function of tissues and organs of the body will be beneficial in the imaging-omics field.
    Full-text · Article · Mar 2014
  • Source
    • "Magnetic resonance (MR) imaging is a superior molecular imaging technique for clinical diagnosis of cancer because it provides noninvasive tomographic imaging with high spatial resolution [1,2]. The sensitivity of MR imaging has significantly improved in recent years by using magnetic nanocrystal (MNC) because an enhanced T2 shortening effect is ascribed to the high crystallinity of MNC [3-5]. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Nucleic acid-based aptamers have been developed for the specific delivery of diagnostic nanoprobes. Here, we introduce a new class of smart imaging nanoprobe, which is based on hybridization of a magnetic nanocrystal with a specific aptamer for specific detection of the angiogenic vasculature of glioblastoma via magnetic resonance (MR) imaging. The magnetic nanocrystal imaging core was synthesized using the thermal decomposition method and enveloped by carboxyl polysorbate 80 for water solubilization and conjugation of the targeting moiety. Subsequently, the surface of the carboxylated magnetic nanocrystal was modified with amine-functionalized aptamers that specifically bind to the vascular growth factor receptor 2 (VEGFR2) that is overexpressed on angiogenic vessels. To assess the targeted imaging potential of the aptamer-conjugated magnetic nanocrystal for VEGFR2 markers, the magnetic properties and MR imaging sensitivity were investigated using the orthotopic glioblastoma mouse model. In in vivo tests, the aptamer-conjugated magnetic nanocrystal effectively targeted VEGFR2 and demonstrated excellent MR imaging sensitivity with no cytotoxicity.
    Full-text · Article · Sep 2013 · Nanoscale Research Letters
Show more