Species dependence on plasma protein binding and relaxivity of the gadolinium-based MRI contrast agent MS-325.
OBJECTIVE
We sought to determine whether there is a species dependence on plasma protein and serum album binding and/or relaxivity of the MR contrast agent MS-325.


METHODS
Equilibrium binding of MS-325 to plasma proteins or purified serum albumin was determined as a function of chelate concentration. T1 and T2 values were determined at 0.47 and 1.41 T, and NMRD profiles were measured to determine the changes in relaxivity over varying field strengths from 0.002 to 1.2 T.


RESULTS
The binding of MS-325 to either animal plasma or serum albumin plateaus at chelate concentrations less than 0.1 mM with human, pig, and rabbit plasmas showing maximum binding. Human and pig plasmas show the greatest observed relaxivity enhancement in the presence of MS-325.


CONCLUSIONS
MS-325 exhibits increased relaxivity in blood plasma as the result of plasma protein binding. Binding ranged from 64% to 91% and was species dependent: human > pig approximately rabbit > dog approximately rat approximately mouse.
EPIX Pharmaceuticals, Cambridge, Massachusetts. 02142-1118, USA.
Harriet B
HB
Eldredge
Marga
M
Spiller
Jaclyn M
JM
Chasse
Matthew T
MT
Greenwood
Peter
P
Caravan
D000818:Animals; D003287:Contrast Media / Q000737:chemistry / Q000493:pharmacokinetics*; D004285:Dogs; D005682:Gadolinium; D006801:Humans; D008279:Magnetic Resonance Imaging; D051379:Mice; D015394:Molecular Structure; D009942:Organometallic Compounds / Q000737:chemistry / Q000493:pharmacokinetics*; D011485:Protein Binding; D011817:Rabbits; D051381:Rats; D012709:Serum Albumin / Q000493:pharmacokinetics; D013045:Species Specificity; D013223:Statistics as Topic; D013552:Swine
D003287:Contrast Media; D009942:Organometallic Compounds; D012709:Serum Albumin; D005682:Gadolinium; C109932:gadofosveset trisodium