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NMR relaxation studies with MnDPDP
T E Southon1, D Grant, A Bjørnerud
1Nycomed Imaging AS, Oslo, Norway.
Purpose:
Our studies were designed to compare the efficacy of mangafodipir trisodium (MnDPDP, Teslascan) as a tissue-specific MR agent with that of manganese chloride (MnCl2), to compare the efficacy of different doses and rates of administration of MnDPDP, and to collect the data needed for predicting optimum pulse sequences.
Material And Methods:
The dose response for the relaxation rates R1 and R2 at 0.47 T, and the manganese (Mn) concentrations in rat liver and in the liver, pancreas, heart and adrenals of pigs was determined for both MnDPDP and MnCl2 administered i.v. Computer simulations were carried out to model the effects of different tissue Mn concentrations and TR on signal intensities and contrast-to-noise ratios.
Results:
In rat liver and pig organs both compounds produced a positive dose-response in R1 and tissue Mn concentration, and only small or no response in R2. The Mn concentration in rat liver was positively correlated with R1, regardless of the form in which Mn was given, or the rate of administration. Optimal imaging parameters are therefore expected to be different pre- and post-MnDPDP administration.
Conclusion:
The added cardiovascular safety of MnDPDP compared with MnCl2 does not result in loss of efficacy in increasing RI at the intended clinical dose of 5 mumol/kg MnDPDP. The changes in R2 were too small to affect T2-weighted images. The data give the basis for choosing the appropriate pulse sequences for MnDPDP-enhanced MR imaging.
Insights
Mangafodipir trisodium (MnDPDP) and manganese chloride (MnCl2) both enhance MRI relaxation rates. MnDPDP offers cardiovascular safety without sacrificing efficacy for T1-weighted imaging.
Area of Science:
- Magnetic Resonance Imaging (MRI)
- Medical Imaging Agents
- Pharmacology
Background:
- Mangafodipir trisodium (MnDPDP) is a potential tissue-specific MRI contrast agent.
- Manganese chloride (MnCl2) is a known MRI contrast agent.
- Comparing the efficacy and optimal administration of MnDPDP versus MnCl2 is crucial for clinical application.
Purpose of the Study:
- To compare the efficacy of MnDPDP as a tissue-specific MR agent against MnCl2.
- To evaluate the impact of different doses and administration rates of MnDPDP.
- To gather data for optimizing MRI pulse sequences with MnDPDP.
Main Methods:
- Determined dose-response for R1 and R2 relaxation rates at 0.47 T for MnDPDP and MnCl2.
- Measured manganese concentrations in rat liver and pig organs (liver, pancreas, heart, adrenals).
- Utilized computer simulations to model effects of tissue Mn concentration and TR on signal intensity and contrast-to-noise ratios.
Main Results:
- Both MnDPDP and MnCl2 showed a positive dose-response for R1 and tissue Mn concentration in rat liver and pig organs.
- R2 relaxation rates showed minimal response to both agents.
- Rat liver Mn concentration correlated positively with R1, irrespective of Mn form or administration rate.
Conclusions:
- MnDPDP provides cardiovascular safety over MnCl2 without compromising efficacy for increasing R1 at the clinical dose of 5 μmol/kg MnDPDP.
- Minimal changes in R2 suggest limited impact on T2-weighted images.
- The study provides a basis for selecting appropriate pulse sequences for MnDPDP-enhanced MRI.