Distribution of TmDOTP5- in rat tissues

TmDOTP5- vs. CoEDTA- as markers of extracellular tissue space

Research output: Contribution to journalArticle

19 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)1800-1805
Number of pages6
JournalJournal of Applied Physiology
Volume85
Issue number5
StatePublished - Nov 1998

Fingerprint

Extracellular Space
Urine
Bone and Bones
Organophosphonates
Liver
Contrast Media
Spectrum Analysis
Myocardium
Pharmacokinetics
Kidney

Keywords

  • Extracellular space marker
  • Intracellular sodium
  • Tissue distribution

ASJC Scopus subject areas

  • Endocrinology
  • Physiology
  • Orthopedics and Sports Medicine
  • Physical Therapy, Sports Therapy and Rehabilitation

Cite this

Distribution of TmDOTP5- in rat tissues : TmDOTP5- vs. CoEDTA- as markers of extracellular tissue space. / Makos, J. D.; Malloy, C. R.; Sherry, A. D.

In: Journal of Applied Physiology, Vol. 85, No. 5, 11.1998, p. 1800-1805.

Research output: Contribution to journalArticle

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abstract = "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.",
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