The
Gd
III-based ma
gnetic resonance ima
gin
g contrast a
gent MS-325 tar
gets the blood protein serum albumin,resultin
g in an increased efficacy (relaxivity) as a relaxation a
gent. MS-325 showed different relaxivities whenbound to serum albumin from different species, e.
g.,
r1 = 30.5 mM
-1 s
-1 (rabbit) vs 46.3 mM
-1 s
-1 (human) at35
ges/entities/de
g.
gif">C and 0.47 T. To investi
gate the mechanism for this difference, surro
gate complexes were prepared where theGd
III ion was replaced by other Ln
III ions. Fluorescence lifetime measurements of the Eu
III analo
gue indicated thatthe hydration number was
q = 1 and did not chan
ge when bound to either human, rat, rabbit, pi
g, or do
g serumalbumin. The Yb
III analo
gue,
YbL1, was prepared and characterized by
1H NMR. Line-shape analysis of theparama
gnetic-shifted
1H NMR resonances in the presence of increasin
g amounts of human (HSA) or rabbit (RSA)serum albumin allowed estimation of the transverse relaxation rate,
R2, of these resonances for the protein-bound
YbL1. The rotational correlation time of
YbL1 was calculated from
R2, and the Yb-H distance and was
ges/
gifchars/tau.
gif" BORDER=0 >
R = 8 ±1 ns when bound to HSA and 13 ± 2 ns when bound to RSA. The water exchan
ge rate at the Dy
III analo
gue,
DyL1, was determined from variable-temperature
R2 measurements at 9.4 T when
DyL1 was bound to either HSAor RSA. At 37
ges/entities/de
g.
gif">C, water exchan
ge at
DyL1 was (31 ± 5) × 10
6 s
-1 when bound to HSA but (3.8 ± 0.2) × 10
6 s
-1when bound to RSA. Slower water exchan
ge upon RSA bindin
g explains the differences in relaxivity observed.The approach of usin
g surro
gate lanthanides to identify specific molecular parameters influencin
g relaxivity is applicableto other protein-tar
geted Gd
III contrast a
gents.