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in rat tissues:
TmDOTP5 vs.
CoEDTA as markers of
extracellular tissue space
1 Department of Chemistry,
The distribution
of TmDOTP5
in rat tissue
was compared with CoEDTA,
an anionic complex previously used as a marker of extracellular space.
Heart, liver, muscle, blood, and urine were collected from rats after
infusion of either complex and were quantitatively analyzed by atomic
absorption spectroscopy. Although total
TmDOTP5 in blood and tissue
was consistently lower (0.88 ± 0.04;
n = 6) than
CoEDTA after an identical
infusion protocol (presumably because of some association of the
phosphonate complex with bone), a comparison of blood and tissue
contents indicated that the two anionic complexes distributed into
identical extracellular spaces. Relative extracellular space in the in
vivo liver, as determined by
TmDOTP5 and
CoEDTA, was 0.18 ± 0.02 and 0.15 ± 0.01, respectively. The corresponding relative
extracellular space values for the in vivo heart reported by the two
agents were identical (0.11 ± 0.02). Experiments were also
performed to evaluate the washout kinetics of
TmDOTP5 from anesthesized
rats. In rats given a total dose of 0.16 mmol TmDOTP5, 81% appeared in
urine by 180 min, <2% was found in all remaining soft tissue,
leaving ~18% undetected. The rate of Tm appearance in urine was fit
to a standard pharmacokinetic model that included four tissue
compartments: plasma, one fast equilbrating space, one slow
equilibrating space, and one very slow equilibrating space (presumably
bone). The best fit result suggests that the highly charged
TmDOTP5 complex is cleared
from plasma more rapidly than is the typical lower charged Gd-based
contrast agents and that release from bone is slow compared with renal clearance.
extracellular space marker; intracellular sodium; tissue distribution
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