Article

In vivo imaging with a cell-permeable porphyrin-based MRI contrast agent.

Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
Chemistry & biology (Impact Factor: 6.52). 06/2010; 17(6):665-73. DOI: 10.1016/j.chembiol.2010.05.009
Source: PubMed

ABSTRACT Magnetic resonance imaging (MRI) with molecular probes offers the potential to monitor physiological parameters with comparatively high spatial and temporal resolution in living subjects. For detection of intracellular analytes, construction of cell-permeable imaging agents remains a challenge. Here we show that a porphyrin-based MRI molecular imaging agent, Mn-(DPA-C(2))(2)-TPPS(3), effectively penetrates cells and persistently stains living brain tissue in intracranially injected rats. Chromogenicity of the probe permitted direct visualization of its distribution by histology, in addition to MRI. Distribution was concentrated in cell bodies after hippocampal infusion. Mn-(DPA-C(2))(2)-TPPS(3) was designed to sense zinc ions, and contrast enhancement was more pronounced in the hippocampus, a zinc-rich brain region, than in the caudate nucleus, which contains relatively little labile Zn(2+). Membrane permeability, optical activity, and high relaxivity of porphyrin-based contrast agents offer exceptional functionality for in vivo imaging.

0 Bookmarks
 · 
110 Views
  • [Show abstract] [Hide abstract]
    ABSTRACT: A supramolecular polymer is first constructed through the intermolecular inclusion complexation of bridged bis(permethyl-β-cyclodextrin) (1) with MnIII-porphyrin bearing poly(ethylene glycol) (PEG) side chains (MnIII-TPP) and characterized by UV/vis absorption spectroscopy, NMR, dynamic light scattering (DLS), atomic force microscopy (AFM), and transmission electron microscopy (TEM). MnIII-TPP in the supramolecular polymer 1·MnIII-TPP would be reduced effectively to a higher electronic spins MnII-TPP by sodium ascorbate, but free MnIII-TPP cannot be reduced in the same condition. The toxicity of the supramolecular polymer in vitro and the magnetic resonance imaging effectiveness both in vitro and in vivo are estimated, and the results obtained not only demonstrate the supramolecular polymer to have no cellular toxicity but also show the MR signal enhancement.
    Macromolecules 05/2013; 46(11):4268–4275. · 5.93 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: The field of imaging science is growing immensely, with the emergence of “noninvasive” in vivo imaging technologies and imaging probes like Positron Emission Tomography (PET), Fluorescence Imaging (FI) and Magnetic Resonance Imaging (MRI), to observe events at molecular and cellular levels, and consequently to speed up drug development processes. For instance, the imaging of cancer specific molecular targets ought to permit precocious diagnosis and superior evaluation to oncology patients. Porphyrins and their derivatives (or related compounds, like phthalocyanines) represent one of the oldest, most widely studied chemical structures, both in nature and in biomedical applications. They display intrinsic affinity for tumor localization and their well-portrayed photophysical and photosensitizing properties can lead to their potential use as sensitizer in a variety of in vivo imaging technologies. This contribution will review recent developments involving tetrapyrrolic -based sensitizers for cancer detection, with emphasis on PET, FI and MRI technologies.
    Current Organic Synthesis 05/2014; 11(1). · 2.44 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Photodynamic therapy (PDT) is a site-specific treatment of cancer involving the administration of a photosensitizer (PS) followed by the local light activation. Besides efficient PSs, image guidance is essential for precise and safe light delivery to the targeting site, thus improving the therapeutic effectiveness. Herein, we report the fabrication of theranostic porphyrin dyad nanoparticles (TPD NPs) for magnetic resonance imaging (MRI)-guided PDT cancer therapy, where the inner metal free porphyrin functions as a photosensitizer for PDT while the outer Mn-porphyrin serve as an MRI contrast agent. Covalent attachment of porphyrins to TPD NPs avoids premature release during systemic circulation. In addition, TPD NPs (~60 nm) could passively accumulate in tumors and be avidly taken up by tumor cells. The PDT and MRI capabilities of TPD NPs can be conveniently modulated by varying the molar ratio of metal free porphyrin/Mn-porphyrin. At the optimal molar ratio of 40.1%, the total drug loading content is up to 49.8%, 31.3% for metal free porphyrin and 18.5% for Mn-porphyrin. The laser light ablated the tumor completely within 7 days in the presence of TPD NPs and the tumor growth inhibition was 100%. The relaxivities were determined to be 20.58 s−1 mm−1 for TPD NPs, about four times as much as that of Mn-porphyrin (5.16 s−1 mm−1). After 24 h intravenous injection of TPD NPs, MRI images showed that the whole tumor area remained much brighter than surrounding healthy tissue, allowing to guide the laser light to the desired tumor site for photodynamic ablation.
    Biomaterials 08/2014; 35(24):6379–6388. · 8.31 Impact Factor

Full-text (2 Sources)

Download
66 Downloads
Available from
May 27, 2014