Elsevier

Neuropharmacology

Volume 30, Issue 3, March 1991, Pages 283-292
Neuropharmacology

Metabolism of 99mTc-l,l-Ethyl cysteinate dimer in healthy volunteers

https://doi.org/10.1016/0028-3908(91)90156-6Get rights and content

Abstract

99mTc-l,l-Ethyl cysteinate dimer (ECD) is a brain-perfusion imaging agent, which exhibits selective retention in brain and rapid renal excretion. The pharmacokinetics and metabolism of ECD were studied in vivo in healthy humans and its metabolism in vitro was evaluated in tissue from human brain. In vitro studies showed 99mTc-l,l-ECD to be metabolized to a polar 99mTc-complex. It has been shown previously that most of the activity of 99mTo retained in the brain of the monkey in vivo is in the form of a polar 99mTc complex (Walovitch, Hill, Garrity, Cheesman, Burgess, O'Leary, Watson, Ganey, Morgan and Williams, 1989). Whole body images of the distribution of 99mTc-l,l-ECD (10mCi i.v.) in four adult males showed good uptake in brain, with slow elimination (6.8 ± 0.3% injected dose [mean ± SE] at 5 min), with less than 25% decrease in activity during 4 hr of imaging. Background areas in the head and lungs washed out rapidly, providing ideal imaging conditions. Elimination of 99mTc from venous blood was biphasic, with a plateau of activity between 2–15 min (7–8% injected dose) before a terminal phase, with a t12 of a few hours. Organic extraction of whole venous blood showed greater than 50% of the 99mTc-l,l-ECD to be in the form of polar metabolite(s) at 5 min. They were identified in the urine as the 99mTc ethylenediylbis-l-cysteine, monoethyl ester complex (ECM) and the 99mTc-ethylenediybis-l-cysteine complex (EC). These metabolites were excreted rapidly (75% injected dose in urine within 6hr).

The results of this study support the hypothesis that the selective retention in brain, rapid blood elimination and renal excretion of 99mTc-l,l-ECD is due to its metabolic transformation to polar end products.

References (22)

  • P. Bergstein et al.

    Ester substituted diamine-dithiol radiolabeled complexes thereof

    (1987)
  • P. Blondeau et al.

    Dimerization of an intermediate during the sodium in liquid ammonium reduction of l-thiazolidine-4-carboxylic acid

    Can. J. Chem.

    (1967)
  • G. Borman et al.

    Metabolism of Tc99m-ECD in isolated rat organs

    J. nucl. Med.

    (1989)
  • S. Brimijoin et al.

    Immuno-chemistry of mammalian cholinesterases

  • A.P. Carpenter et al.

    Characterization and use of a gamma radiation TLC scanner for radiochemical purity measurements of radiopharmaceutical kit preparations of 99mTc(dmpe)2Cl2+

    J. Radioanalyt. nucl. Chem.

    (1985)
  • R.E. Catalan et al.

    Temperature effects of cholinesterases from rat brain capillaries

    Biosci. Rep.

    (1986)
  • D.S. Edwards et al.

    Synthesis and characterization of technetium and rhenium complexes of N,N'-ethylenediylbis-l-cysteine-Neurolite® and its metabolites

    Technetium Chem. nucl. Med.

    (1990)
  • P.J. Ell et al.

    First results of a comparison between 99mTc-ECD and 99mTc-HMPAO

    J. nucl. Med.

    (1988)
  • B.A. Flumerfelt et al.

    Cholinesterase of capillaries in the rat brain. A light and electron microscopic study

    Histochem. J.

    (1973)
  • M. Franceschi et al.

    Brain washout of Tc-99m-l,l-ethyl cysteinate dimer (ECD) in normal volunteers

    Eur. J. nucl. Med.

    (1988)
  • K. Garretty et al.

    A comparison of regional cerebral blood flow with Xe-133 to SPECT Tc-99m-ECD

    J. nucl. Med.

    (1988)
  • Cited by (76)

    • Persistent brain damage in reversible cerebral vasoconstriction syndrome on <sup>99m</sup>Tc-ethyl cysteinate dimer single-photon emission computed tomography: A long-term observational study

      2022, Journal of the Neurological Sciences
      Citation Excerpt :

      There are three representative SPECT tracers: 99mTc-ECD, N-isopropyl-123I-ρ-iodoamphetamine, and 99mTc-d, l-hexamethyl-propyleneamine oxime [20,21]. Although all these tracers share a common hydrophobic nature, 99mTc-ECD differs from the other tracers in that it is converted to its hydrophilic form just after passing through the BBB and entering the brain tissue [22]. Furthermore, 99mTc-ECD is retained for a certain period in normal brain tissue with an intact BBB and is washed out immediately in the case of a damaged BBB or brain tissue [23].

    • Quantitation of rat cerebral blood flow using <sup>99m</sup>Tc-HMPAO

      2017, Nuclear Medicine and Biology
      Citation Excerpt :

      Two 99mTc-labeled tracers, Tc-99m-hexamethylpropyleneamine oxime (99mTc-exametazime, 99mTc-HMPAO) and Tc-99m-L,L-ethyl cysteinate dimer (99mTc-ECD), are frequently used for clinical CBF assessment. After intravenous injection of 99mTc-HMPAO and 99mTc-ECD, they are taken up by the brain, distributed according to regional CBF and converted to hydrophilic forms, which are retained for long time in the brain [5,6]. Conversion of 99mTc-ECD to hydrophilic forms is accomplished via ester hydrolysis by esterase [7].

    • Peri-ictal single-photon emission computed tomography: Principles and applications in epilepsy evaluation

      2012, Handbook of Clinical Neurology
      Citation Excerpt :

      This prevented prompt injection of 99mTc-HMPAO during the ictal period and has resulted in most injections being conducted during the postictal period. 99mTc-labeled ethyl cysteinate diethylester (99mTc-ECD) was later developed as a preconstituted stable radiotracer, ready for immediate injection when a seizure occurs (Walovitch et al., 1991). Thus, 99mTc-ECD can be injected more quickly after seizure onset than 99mTc-HMPAO (O'Brien et al., 1999a).

    • Subtraction ictal SPECT coregistered to MRI for seizure focus localization in partial epilepsy

      2000, Mayo Clinic Proceedings
      Citation Excerpt :

      However, ETLE is less well understood, and the new localizing techniques such as ictal SPECT and SISCOM have the potential to be of most value in these patients. First reported in 1988 by Cheesman et al44 and by Walovitch et al,45,46 99mTc-ECD was approved by the Food and Drug Administration in 1994 for stroke imaging. However, because of ECD's greater chemical stability compared with HMPAO,99mTc-ECD quickly became used for seizure imaging and other physician-directed applications.47–50

    View all citing articles on Scopus
    View full text