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

J Magn Reson Imaging. 2014 Dec;40(6):1474-80. doi: 10.1002/jmri.24483. Epub 2013 Nov 8.

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.

Keywords: cardiovascular imaging; dynamic contrast-enhanced (DCE) MRI; liver imaging; permeability imaging; pharmacokinetics; positive contrast MRI contrast agents.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Contrast Media / pharmacokinetics
  • Female
  • Magnesium Compounds / pharmacokinetics*
  • Magnetic Resonance Imaging / methods*
  • Metabolic Clearance Rate
  • Organ Specificity / physiology
  • Porphyrins / pharmacokinetics*
  • Rats
  • Rats, Long-Evans
  • Tissue Distribution
  • Whole Body Imaging / methods*

Substances

  • Contrast Media
  • Magnesium Compounds
  • Porphyrins