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Mitochondrial localization and characterization of 99Tc-SESTAMIBI in heart cells by electron probe X-ray microanalysis and 99Tc-NMR spectroscopy.

Publication ,  Journal Article
Piwnica-Worms, DP; Kronauge, JF; LeFurgey, A; Backus, M; Hockett, D; Ingram, P; Lieberman, M; Holman, BL; Jones, AG; Davison, A
Published in: Magn Reson Imaging
1994

As the development of targeted intracellular magnetic resonance contrast agents proceeds, techniques for the quantitative analysis of the subcellular compartmentation and characterization of metallopharmaceuticals must also advance. To this end, the subcellular distribution and chemical state of hexakis (2-methoxyisobutyl isonitrile) technetium-99 (99Tc-SESTAMIBI), the ground state of the organotechnetium radiopharmaceutical used for the noninvasive evaluation of myocardial perfusion and viability by scintigraphy, has been determined by a novel application of electron probe X-ray microanalysis (EPXMA) and 99Tc-NMR spectroscopy. In cryopreserved cultured chick heart cells equilibrated in 36 microM 99Tc-SESTAMIBI, EPXMA imaging of mitochondria yielded a respiratory uncoupler-sensitive characteristic 99Tc X-ray peak representing 32.0 +/- 2.9 nmoles Tc/mg dry weight, while EPXMA of cytoplasm or nucleus showed no peak significantly greater than the threshold detectability limit of approximately 1 nmole/mg dry weight. Technetium-99 NMR spectroscopy of heart cells equilibrated with 99Tc-SESTAMIBI showed a single peak at -45.5 ppm with no evidence of significant line broadening or chemical shift compared to aqueous chemical standards, indicating that the majority of the complex exists unbound within the mitochondrial matrix. These data quantitatively demonstrate the localization of this lipophilic cationic organometallic complex within mitochondria in situ, consistent with a sequestration mechanism dependent on membrane potentials. Furthermore, this study establishes the general feasibility of combined EPXMA and NMR spectroscopy for the direct subcellular localization and characterization of metallopharmaceuticals, techniques that are readily applicable to MR contrast agents.

Duke Scholars

Published In

Magn Reson Imaging

DOI

ISSN

0730-725X

Publication Date

1994

Volume

12

Issue

4

Start / End Page

641 / 652

Location

Netherlands

Related Subject Headings

  • Technetium Tc 99m Sestamibi
  • Technetium
  • Sodium
  • Potassium
  • Nuclear Medicine & Medical Imaging
  • Myocardium
  • Mitochondria, Heart
  • Microscopy, Electron
  • Magnetic Resonance Spectroscopy
  • Electron Probe Microanalysis
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Piwnica-Worms, D. P., Kronauge, J. F., LeFurgey, A., Backus, M., Hockett, D., Ingram, P., … Davison, A. (1994). Mitochondrial localization and characterization of 99Tc-SESTAMIBI in heart cells by electron probe X-ray microanalysis and 99Tc-NMR spectroscopy. Magn Reson Imaging, 12(4), 641–652. https://doi.org/10.1016/0730-725x(94)92459-7
Piwnica-Worms, D. P., J. F. Kronauge, A. LeFurgey, M. Backus, D. Hockett, P. Ingram, M. Lieberman, B. L. Holman, A. G. Jones, and A. Davison. “Mitochondrial localization and characterization of 99Tc-SESTAMIBI in heart cells by electron probe X-ray microanalysis and 99Tc-NMR spectroscopy.Magn Reson Imaging 12, no. 4 (1994): 641–52. https://doi.org/10.1016/0730-725x(94)92459-7.
Piwnica-Worms DP, Kronauge JF, LeFurgey A, Backus M, Hockett D, Ingram P, et al. Mitochondrial localization and characterization of 99Tc-SESTAMIBI in heart cells by electron probe X-ray microanalysis and 99Tc-NMR spectroscopy. Magn Reson Imaging. 1994;12(4):641–52.
Piwnica-Worms, D. P., et al. “Mitochondrial localization and characterization of 99Tc-SESTAMIBI in heart cells by electron probe X-ray microanalysis and 99Tc-NMR spectroscopy.Magn Reson Imaging, vol. 12, no. 4, 1994, pp. 641–52. Pubmed, doi:10.1016/0730-725x(94)92459-7.
Piwnica-Worms DP, Kronauge JF, LeFurgey A, Backus M, Hockett D, Ingram P, Lieberman M, Holman BL, Jones AG, Davison A. Mitochondrial localization and characterization of 99Tc-SESTAMIBI in heart cells by electron probe X-ray microanalysis and 99Tc-NMR spectroscopy. Magn Reson Imaging. 1994;12(4):641–652.
Journal cover image

Published In

Magn Reson Imaging

DOI

ISSN

0730-725X

Publication Date

1994

Volume

12

Issue

4

Start / End Page

641 / 652

Location

Netherlands

Related Subject Headings

  • Technetium Tc 99m Sestamibi
  • Technetium
  • Sodium
  • Potassium
  • Nuclear Medicine & Medical Imaging
  • Myocardium
  • Mitochondria, Heart
  • Microscopy, Electron
  • Magnetic Resonance Spectroscopy
  • Electron Probe Microanalysis