Masahito Mikawa

Nagoya University, Nagoya, Aichi, Japan

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Publications (7)11.14 Total impact


  • No preview · Article · Sep 2002 · Academic Radiology

  • No preview · Article · Jun 2002 · Academic Radiology
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    ABSTRACT: Water-soluble gadolinium (Gd) endohedral metallofullerenes have been synthesized as polyhydroxyl forms (Gd@C(82)(OH)(n)(), Gd-fullerenols) and their paramagnetic properties were evaluated by in vivo as well as in vitro for the novel magnetic resonance imaging (MRI) contrast agents for next generation. The in vitro water proton relaxivity, R(1) (the effect on 1/T(1)), of Gd-fullerenols is significantly higher (20-folds) than that of the commercial MRI contrast agent, Magnevist (gadolinium-diethylenetriaminepentaacetic acid, Gd-DTPA) at 1.0 T close to the common field of clinical MRI. This unusually high proton relaxivity of Gd-fullerenols leads to the highest signal enhancement at extremely lower Gd concentration in MRI studies. The strong signal was confirmed in vivo MRI at lung, liver, spleen, and kidney of CDF1 mice after i.v. administration of Gd-fullerenols at a dose of 5 micromol Gd/kg, which was 1/20 of the typical clinical dose (100 micromol Gd/kg) of Gd-DTPA.
    No preview · Article · Jul 2001 · Bioconjugate Chemistry
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    ABSTRACT: Various water-soluble multi-hydroxyl fullerenes (fullerenols), C60(OH)n, C70(OH)n and C84(OH)n, and a Gd metallo-fullerenols, Gd@C82(OH)n have been synthesized by the Kitazawa method. Elementary chemical analyses indicate that all of these fullerenols have 30–40 hydroxyl groups and 11–15 coordinated water molecules via hydrogen bonds. Electron energy loss spectroscopy (EELS) on Gd@C82 fullerenols shows that the peak area in the C K-edge spectra decreases on going from intact Gd@C82 metallofullerene to Gd@C82 fullerenols, indicating an increase in sp3 character of the fullerenols. Furthermore, Gd M4,5-edge EELS spectra show that the encapsulated Gd atom has a trivalent Gd3+ state.
    Preview · Article · Jul 2000 · Chemical Physics Letters
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    ABSTRACT: In clinical diagnosis, gadolinium (Gd) ion/low molecular weight chelater complexes have been used as MRI contrast agents that disperse throughout a particular tissue and cause a brighter appearance in MRI. In order to provide a novel imaging concept for MRI, a contrast agent in which the T(1)-relaxation shortening activity (R(1) relaxivity) changes in response to the pH differences was studied. We prepared a polyion complex (PIC) consisting of a polyanionic Gd-chelater, poly(diethylenetriamine-N,N,N',N", N"-pentaaceto, DTPA) (1,3-propanediamide) (denoted as 1a) loaded with Gd ions at a [Gd]/[DTPA unit] ratio of 0.2 (denoted as 1b), and a polycation, poly[2-(diethylamino)ethyl methacrylate] (denoted as 2). The stoichiometric (based on ionic groups) mixture of 1b and 2 formed complex coacervates from pH 5 to pH 8. The R(1) relaxivity of Gd(3+) in the complex was considerably influenced by the pH, and the relative signal intensity changed from 4 at pH 7.2 to 11 at pH 5.0, as determined by an MRI phantom study. The pH responsivity of the complex solution varied with the composition of the PIC (i.e., the mixing ratio of 1b and 2), allowing us to modulate the pH sensibility. The ionic charge balance and swelling of PIC seemingly were related to the pH-dependent R(1) relaxivity change. It is expected that the PIC-based MRI contrast agent may provide a novel category of MRI methods and be useful in improving the detectability of an MRI-based diagnosis.
    No preview · Article · Apr 2000 · Journal of Biomedical Materials Research
  • Masahito Mikawa · Naoto Miwa · Toshihiro Akaike · Atsushi Maruyama
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    ABSTRACT: In clinical diagnosis, gadolinium (Gd) ion/low molecular weight chelater complexes have been used as MRI contrast agents that disperse throughout a particular tissue and cause a brighter appearance in MRI. In order to provide a novel imaging concept for MRI, a contrast agent in which the T1-relaxation shortening activity (R1 relaxivity) changes in response to the pH differences was studied. We prepared a polyion complex (PIC) consisting of a polyanionic Gd-chelater, poly(diethylenetriamine-N,N,N′,N″,N″-pentaaceto, DTPA) (1,3-propanediamide) (denoted as 1a) loaded with Gd ions at a [Gd]/[DTPA unit] ratio of 0.2 (denoted as 1b), and a polycation, poly[2-(diethylamino)ethyl methacrylate] (denoted as 2). The stoichiometric (based on ionic groups) mixture of 1b and 2 formed complex coacervates from pH 5 to pH 8. The R1 relaxivity of Gd3+ in the complex was considerably influenced by the pH, and the relative signal intensity changed from 4 at pH 7.2 to 11 at pH 5.0, as determined by an MRI phantom study. The pH responsivity of the complex solution varied with the composition of the PIC (i.e., the mixing ratio of 1b and 2), allowing us to modulate the pH sensibility. The ionic charge balance and swelling of PIC seemingly were related to the pH-dependent R1 relaxivity change. It is expected that the PIC-based MRI contrast agent may provide a novel category of MRI methods and be useful in improving the detectability of an MRI-based diagnosis. © 2000 John Wiley & Sons, Inc. J Biomed Mater Res, 49, 390–395, 2000.
    No preview · Article · Mar 2000 · Journal of Biomedical Materials Research
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    ABSTRACT: A pH-sensitive MRI contrast agent whose signal intensity is activated only at the lower pH was newly designed to establish a novel imaging concept which depict microenvironment differences in pathophysiological features of damaged tissues.
    No preview · Article · Jul 1998 · Chemistry Letters

Publication Stats

430 Citations
11.14 Total Impact Points

Institutions

  • 2002
    • Nagoya University
      • Department of Chemistry
      Nagoya, Aichi, Japan
  • 1998-2002
    • Tokyo Institute of Technology
      • Department of Biomolecular Engineering
      Edo, Tokyo, Japan