All measurements were
taken on a Bruker Minispec instrument at 60 MHz following a modified
protocol described by Laurent et al.12 (link),13 (link) The following
commercial GBCAs were individually prepared: gadobutrol (Gadovist,
Germany, Bayer), gadoteric acid (Dotarem, France, Guerbet), gadoteridol
(Prohance, Italy, Bracco), gadoxetic acid (Eovist, Germany, Bayer),
gadopentetic acid (Magnevist, Germany, Bayer), gadodiamide (Omniscan,
United States, GE Healthcare), gadofosveset (Ablavar, United States,
Lantheus), and gadobenic acid (Multihance, Italy, Bracco). All solutions
and vessels were warmed to 37.5 °C prior to reaction and measurement.
The experiment was initiated by adding 125 μL of aqueous ZnCl2 to an NMR tube containing 250 μL of phosphate buffer
solution (pH 7.4, divalent metal-free) and 125 μL of the GBCA
being analyzed. The final concentrations of GBCA and ZnCl2 were 2.5 mM, and the final concentration of phosphate buffer was
10 mM. Initial measurements were acquired within 1 min of adding ZnCl2, shaking, and sealing the tube. The same conditions were
replicated for Gd[DTPA-cs124]. Using an inversion recovery sequence,
repetitive T1 measurements were performed
every 6 h at 37.5 °C for each sample for a total of 96 h, and
all GBCAs were measured in triplicate. From the T1 values acquired in the stability assay, R1 values at each time point were calculated, normalized
against the R1 value of each GBCA at 2.5
mM, and plotted as a function of time. The stability ratio was calculated
for each GBCA by taking the ratio of the average measurement at 96
h over the initial measurement at 0 h.