Institute of Clinical Physiology, Consiglio Nazionale delle Ricerche (CNR), Via Moruzzi, 1, 56124, Pisa, Italy.
Fondazione Toscana G. Monasterio, Via Moruzzi, 1, 56124, Pisa, Italy.
Mol Imaging Biol. 2019 Jun;21(3):482-490. doi: 10.1007/s11307-018-1269-9.
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-[I]iodobenzylguanidine ([I]MIBG) myocardial uptake.
Experiments were performed on animals injected with [I]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.
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 [I]MIBG uptake revealed an analogous trend, showing a good linear relationship with NET expression. Parallel results were obtained from the ex vivo study.
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 [I]MIBG uptake. Moreover, the correlation and the agreement between measurements of regional expression of NET variants and [I]MIBG uptake represent a relevant finding for inferences about NET expression in the context of clinical imaging.
本研究旨在评估健康猪左心室(LV)中心脏去甲肾上腺素转运体(NET)的表达及其与局部 meta-[I]碘苄胍([I]MIBG)心肌摄取的关系。
在注射[I]MIBG 后 2 小时,使用超快速 CZT 伽马相机对动物进行实验,以评估局部心肌摄取。图像采集后,处死动物;迅速取出心脏,并进行体外单光子发射断层扫描(SPECT)成像。然后从左心室中壁和心尖采集四个小组织样本;评估 NET 密度,并进一步根据每个心脏区域的蛋白负荷进行归一化。
检测到三种不同分子量的 NET 蛋白变体。NET 在 LV 中的表达不均匀,下壁密度最高,心尖区域最低。区域内 [I]MIBG 摄取显示出类似的趋势,与 NET 表达呈良好的线性关系。体外研究也得到了类似的结果。
本研究阐明了三种不同变体的 NET 蛋白在健康猪左心室心肌中的表达。NET 在 LV 中的表达不均匀,与区域 [I]MIBG 摄取的差异相平行。此外,NET 变体的区域表达和 [I]MIBG 摄取的测量之间的相关性和一致性代表了在临床成像背景下推断 NET 表达的重要发现。