Stability and transmetallation of the magnetic resonance contrast agent MnDPDP measured by EPR.
MnDPDP [manganese(II) N, N'-dipyridoxylethylenediamine- N, N'-diacetate-5,5'-bis(phosphate)] is the active component of Teslascan, a contrast medium for magnetic resonance imaging of the liver. It has previously been shown that MnDPDP is rapidly dephosphorylated to the monophosphate MnDPMP and the non-phosphorylated MnPLED, and that all these substances are rapidly transmetallated to the corresponding Zn complexes. In the present study we used EPR at 9 and 230 GHz to show that no free Mn(2+) ions can be detected in the product or in a mixture of MnDPDP and human serum. Competition experiments between MnDPDP and Zn(2+), Ca(2+), and Mg(2+) ions revealed approximately 15% transmetallation with Zn(2+) in a buffer system containing metal ion concentrations similar to that in serum, whereas approximately 10% transmetallation was obtained with Ca(2+) and only negligible transmetallation was obtained with Mg(2+) under these conditions. Binding experiments with Mn(2+) added to human albumin and human serum indicate that albumin accounts for most of the protein-bound Mn(2+) in serum.
Schmidt
Peter P
PP
Department of Biochemistry, University of Oslo, Norway.
Toft
Kim G
KG
Skotland
Tore
T
Andersson
KristofferK
K
D001667:Binding, Competitive; D001711:Biotransformation; D002413:Cations, Divalent / Q000032:analysis / Q000378:metabolism; D003287:Contrast Media / Q000737:chemistry* / Q000493:pharmacokinetics; D004355:Drug Stability; D004492:Edetic Acid / Q000031:analogs & derivatives* / Q000097:blood / Q000737:chemistry* / Q000493:pharmacokinetics; D004578:Electron Spin Resonance Spectroscopy; D006801:Humans; D008279:Magnetic Resonance Imaging / Q000379:methods; D008345:Manganese / Q000032:analysis / Q000493:pharmacokinetics*; D011485:Protein Binding; D011732:Pyridoxal Phosphate / Q000031:analogs & derivatives* / Q000097:blood / Q000737:chemistry* / Q000493:pharmacokinetics; D012709:Serum Albumin / Q000378:metabolism
D002413:Cations, Divalent; D003287:Contrast Media; D012709:Serum Albumin; D008345:Manganese; D011732:Pyridoxal Phosphate; D004492:Edetic Acid; C060076:N,N'-bis(pyridoxal-5-phosphate)ethylenediamine-N,N'-diacetic acid