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


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.


CONCLUSIONS
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.
Physiology and Experimental Medicine and Diagnostic Imaging, Hospital for Sick Children, Toronto, Canada; Department of Medical Biophysics, University of Toronto, Toronto, Canada; Institute of Biomaterials and Biomedical Engineering, University of Toronto, Toronto, Canada; Leslie Dan Faculty of Pharmacy, University of Toronto, Toronto, Canada.
Hai-Ling Margaret
HL
Cheng
Inga E
IE
Haedicke
Weiran
W
Cheng
Joris
J
Tchouala Nofiele
Xiao-an
XA
Zhang
D000818:Animals; D003287:Contrast Media / Q000493:pharmacokinetics; D005260:Female; D017616:Magnesium Compounds / Q000493:pharmacokinetics*; D008279:Magnetic Resonance Imaging / Q000379:methods*; D008657:Metabolic Clearance Rate; D009928:Organ Specificity / Q000502:physiology; D011166:Porphyrins / Q000493:pharmacokinetics*; D051381:Rats; D020318:Rats, Long-Evans; D014018:Tissue Distribution; D051598:Whole Body Imaging / Q000379:methods*
D003287:Contrast Media; D017616:Magnesium Compounds; D011166:Porphyrins
cardiovascular imaging; dynamic contrast-enhanced (DCE) MRI; liver imaging; permeability imaging; pharmacokinetics; positive contrast MRI contrast agents