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Uptake mechanisms of meta-[123I]iodobenzylguanidine in isolated rat heart.

Publication ,  Journal Article
Degrado, TR; Zalutsky, MR; Vaidyanathan, G
Published in: Nucl Med Biol
January 1995

In order to clarify the uptake and retention mechanisms of radioiodinated meta-iodobenzylguanidine (MIBG) in heart, the kinetics of no-carrier-added [123I]MIBG were studied in the isolated working rat heart in interaction with pharmacologic agents. The tracer was administered in the perfusate as a 10-min pulse, followed by a 90-min washout period. Kinetic analysis of the externally monitored time-activity curves of control hearts showed avid uptake (Ki = 4.4 +/- 0.7 mL/min/g), and monoexponential clearance (ko = 0.0056 +/- 0.0017 l/min), indicating a distribution volume (Vd = Ki/ko) of 834 +/- 214 mL/g. Blocking experiments (n = 41) were performed with neuronal uptake (uptake-1) inhibitor desipramine (DMI; 50-100 nM) and the extraneuronal uptake (uptake-2) inhibitor N-(9-fluorenyl)-N-methyl-beta-chloroethylamine (SKF550; 0.4-0.8 microM). Uptake rate was 27% reduced (P < 0.05) by 50 nM DMI but not significantly affected by 0.4 microM SKF550. Distribution volume was 88% reduced (P < 0.0005) by 50 nM DMI and 28% reduced (P < 0.05) by 0.4 microM SKF550. In DMI-blocked hearts, uptake rate was dramatically decreased (-80%, P < 0.0005) by SKF550 (0.4 microM), indicating uptake-2 transport contributed predominantly to the extraneuronal uptake of the tracer. The slow uptake rate seen with concomitant inhibition of uptake-1 and uptake-2 was further decreased by addition of unlabeled MIBG (1-10 microM) in a concentration-dependent manner, yet unaffected by addition of the vesicular uptake inhibitor Ro 4-1284 (1 microM). Thus, the uptake rate of [123I]MIBG is primarily dependent on uptake-1 and uptake-2 activity. Other possible mechanisms of uptake such as passive diffusion in association with intracellular binding are significant only in conditions where uptake-1 and uptake-2 mechanisms are largely inhibited.

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Published In

Nucl Med Biol

DOI

ISSN

0969-8051

Publication Date

January 1995

Volume

22

Issue

1

Start / End Page

1 / 12

Location

United States

Related Subject Headings

  • Sympatholytics
  • Rats, Sprague-Dawley
  • Rats
  • Perfusion
  • Nuclear Medicine & Medical Imaging
  • Myocardium
  • Iodobenzenes
  • Iodine Radioisotopes
  • Hemodynamics
  • Female
 

Citation

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Degrado, T. R., Zalutsky, M. R., & Vaidyanathan, G. (1995). Uptake mechanisms of meta-[123I]iodobenzylguanidine in isolated rat heart. Nucl Med Biol, 22(1), 1–12. https://doi.org/10.1016/0969-8051(94)00084-w
Degrado, T. R., M. R. Zalutsky, and G. Vaidyanathan. “Uptake mechanisms of meta-[123I]iodobenzylguanidine in isolated rat heart.Nucl Med Biol 22, no. 1 (January 1995): 1–12. https://doi.org/10.1016/0969-8051(94)00084-w.
Degrado TR, Zalutsky MR, Vaidyanathan G. Uptake mechanisms of meta-[123I]iodobenzylguanidine in isolated rat heart. Nucl Med Biol. 1995 Jan;22(1):1–12.
Degrado, T. R., et al. “Uptake mechanisms of meta-[123I]iodobenzylguanidine in isolated rat heart.Nucl Med Biol, vol. 22, no. 1, Jan. 1995, pp. 1–12. Pubmed, doi:10.1016/0969-8051(94)00084-w.
Degrado TR, Zalutsky MR, Vaidyanathan G. Uptake mechanisms of meta-[123I]iodobenzylguanidine in isolated rat heart. Nucl Med Biol. 1995 Jan;22(1):1–12.
Journal cover image

Published In

Nucl Med Biol

DOI

ISSN

0969-8051

Publication Date

January 1995

Volume

22

Issue

1

Start / End Page

1 / 12

Location

United States

Related Subject Headings

  • Sympatholytics
  • Rats, Sprague-Dawley
  • Rats
  • Perfusion
  • Nuclear Medicine & Medical Imaging
  • Myocardium
  • Iodobenzenes
  • Iodine Radioisotopes
  • Hemodynamics
  • Female