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Gadolinium-free T1 contrast agents for MRI: Tunable pharmacokinetics of a new class of manganese porphyrins

Authors

  • Hai-Ling Margaret Cheng PhD,

    Corresponding author
    1. Physiology and Experimental Medicine and Diagnostic Imaging, Hospital for Sick Children, Toronto, Canada
    2. Department of Medical Biophysics, University of Toronto, Toronto, Canada
    3. Institute of Biomaterials and Biomedical Engineering, University of Toronto, Toronto, Canada
    4. Leslie Dan Faculty of Pharmacy, University of Toronto, Toronto, Canada
    • Address reprint requests to: H.-L.M.C., Hospital for Sick Children, 555 University Ave., Toronto, Ontario, Canada M5G 1X8. E-mail: hailing.cheng@utoronto.ca; X.-a.Z., University of Toronto Scarborough, 1265 Military Trail, Toronto, Ontario, Canada M1C 1A4. E-mail: xazhang@utsc@utoronto.ca

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  • Inga E. Haedicke MSc,

    1. Department of Chemistry, University of Toronto, Toronto, Canada
    2. Department of Physical and Environmental Sciences, University of Toronto Scarborough, Toronto, Canada
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  • Weiran Cheng BSc,

    1. Department of Chemistry, University of Toronto, Toronto, Canada
    2. Department of Physical and Environmental Sciences, University of Toronto Scarborough, Toronto, Canada
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  • Joris Tchouala Nofiele BSc,

    1. Physiology and Experimental Medicine and Diagnostic Imaging, Hospital for Sick Children, Toronto, Canada
    2. Department of Medical Biophysics, University of Toronto, Toronto, Canada
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  • Xiao-an Zhang PhD

    Corresponding author
    1. Department of Chemistry, University of Toronto, Toronto, Canada
    2. Department of Physical and Environmental Sciences, University of Toronto Scarborough, Toronto, Canada
    3. Department of Biological Sciences, University of Toronto Scarborough, Toronto, Canada
    • Address reprint requests to: H.-L.M.C., Hospital for Sick Children, 555 University Ave., Toronto, Ontario, Canada M5G 1X8. E-mail: hailing.cheng@utoronto.ca; X.-a.Z., University of Toronto Scarborough, 1265 Military Trail, Toronto, Ontario, Canada M1C 1A4. E-mail: xazhang@utsc@utoronto.ca

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Abstract

Purpose

To evaluate a new class of manganese porphyrins with tunable pharmacokinetics as potential gadolinium (Gd)-free T1 agents for contrast-enhanced magnetic resonance imaging (MRI).

Materials and Methods

Two new contrast agents, MnTCP and MnP2, were evaluated in four female rats. MRI was performed daily up to 3 days postinjection (0.05 mmol/kg) on a 3 T clinical scanner. T1 relaxation times and dynamic contrast-enhanced MRI were performed to assess contrast enhancement and clearance in blood, heart, liver, kidney, and muscle.

Results

Relative T1 decreases were similar for MnTCP and Gd-DTPA in all tissues but were significantly larger (P < 0.05) for MnP2 in blood, heart, kidney, and liver (2–6-fold larger). Clearance of MnTCP was similar to Gd-DTPA, with T1 returning to baseline by 40 minutes and complete elimination in 1 day. MnP2 was cleared from blood after 2 days and sustained a lowered T1 in other tissues for at least 1 hour (P < 0.05). The maximum enhancement, slope, and time-to-peak were similar between contrast agents. Only the parameter AUC60 differed, with MnP2 yielding the largest AUC60 values primarily through longer retention in tissue.

Conclusion

MnTCP and MnP2 offer distinct applications as Gd-free T1 contrast agents. MnTCP behaves like a Gd-DTPA analog, while MnP2 provides significantly greater and longer positive signal enhancement.J. Magn. Reson. Imaging 2014;40:1474–1480. © 2013 Wiley Periodicals, Inc.

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