Spatial Inhomogeneity of Cardiac Norepinephrine Transport Protein and Meta-[123I]Iodobenzylguanidine Uptake in Swine Myocardial Tissue

Mol Imaging Biol. 2019 Jun;21(3):482-490. doi: 10.1007/s11307-018-1269-9.

Abstract

Purpose: The aim of the present study was to evaluate the expression of the cardiac norepinephrine transporter (NET) in the left ventricle (LV) of healthy pigs and its relationship with regional meta-[123I]iodobenzylguanidine ([123I]MIBG) myocardial uptake.

Procedures: Experiments were performed on animals injected with [123I]MIBG and acquired 2 h later using an ultrafast CZT gamma camera to assess the regional myocardial uptake. After image acquisition, animals were euthanized; the heart was quickly excised and underwent to an ex vivo single photon emission tomography (SPECT) imaging. Four small samples of tissue were then harvested from mid-walls and apex of the left ventricle; NET densities were evaluated and further normalized for protein loading per cardiac region.

Results: Three variants of NET protein with different molecular weights were detected. The expression of NET was not homogenous in the LV, with the highest density in the inferior wall and the lowest one in the apical area. The regional in vivo [123I]MIBG uptake revealed an analogous trend, showing a good linear relationship with NET expression. Parallel results were obtained from the ex vivo study.

Conclusion: This study elucidates the expression of three different variants of NET proteins into the left ventricular myocardium of a healthy pig. NET expression into the LV was not homogeneous and paralleled by differences in regional [123I]MIBG uptake. Moreover, the correlation and the agreement between measurements of regional expression of NET variants and [123I]MIBG uptake represent a relevant finding for inferences about NET expression in the context of clinical imaging.

Keywords: CZT; Cardiac sympathetic innervation; NET; Ultrafast cardiac camera; [123I]MIBG.

MeSH terms

  • 3-Iodobenzylguanidine / metabolism*
  • Animals
  • Heart Ventricles / metabolism
  • Iodine Radioisotopes / chemistry*
  • Myocardium / metabolism*
  • Norepinephrine Plasma Membrane Transport Proteins / metabolism*
  • Perfusion
  • Swine
  • Tomography, Emission-Computed, Single-Photon

Substances

  • Iodine Radioisotopes
  • Norepinephrine Plasma Membrane Transport Proteins
  • 3-Iodobenzylguanidine
  • Iodine-123