NMR relaxation studies with MnDPDP.
OBJECTIVE
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.


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.


CONCLUSIONS
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.
Southon
T E
TE
Nycomed Imaging AS, Oslo, Norway.
Grant
D
D
Bjørnerud
A
A
Moen
O M
OM
Spilling
B
B
Martinsen
I
I
Refsum
H
H
D000818:Animals; D002712:Chlorides / Q000008:administration & dosage / Q000032:analysis / Q000493:pharmacokinetics; D003287:Contrast Media / Q000008:administration & dosage / Q000032:analysis / Q000493:pharmacokinetics*; D004305:Dose-Response Relationship, Drug; D004492:Edetic Acid / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000032:analysis / Q000493:pharmacokinetics; D009682:Magnetic Resonance Spectroscopy / Q000379:methods; D008297:Male; D008345:Manganese / Q000008:administration & dosage / Q000032:analysis / Q000493:pharmacokinetics*; D017895:Manganese Compounds / Q000008:administration & dosage / Q000032:analysis / Q000493:pharmacokinetics; D011732:Pyridoxal Phosphate / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000032:analysis / Q000493:pharmacokinetics; D051381:Rats; D017208:Rats, Wistar; D013054:Spectrophotometry, Atomic; D013552:Swine; D013997:Time Factors; D014018:Tissue Distribution
D002712:Chlorides; D003287:Contrast Media; D017895:Manganese Compounds; D008345:Manganese; D011732:Pyridoxal Phosphate; D004492:Edetic Acid; C060076:N,N'-bis(pyridoxal-5-phosphate)ethylenediamine-N,N'-diacetic acid; C025340:manganese chloride