Mn-citrate and Mn-HIDA: intermediate-affinity chelates for manganese-enhanced MRI.
Mn-citrate and Mn-HIDA: intermediate-affinity chelates for manganese-enhanced MRI.
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DOI：
10.1002/cmmi.1510
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发表时间：
2013-03
影响因子：
--
通讯作者：
Y. Seo;Keitaro Satoh;H. Morita;A. Takamata;Kazuto Watanabe;T. Ogino;T. Hasebe;M. Murakami
中科院分区：
文献类型：
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作者：
Y. Seo;Keitaro Satoh;H. Morita;A. Takamata;Kazuto Watanabe;T. Ogino;T. Hasebe;M. Murakami
在本研究中，我们研究了两种锰络合物，以改善锰增强MRI的图像增强效果，降低游离锰离子的毒性。由于MnClHIDA和低亲和力的₂都与心功能的缓慢持续下降有关，我们研究了中等亲和力的螯合物：N-(2-羟乙基)亚氨基二乙酸锰(Mn-HIDA)和柠檬酸锰。在37℃和4.7T下，人工脑脊液中柠檬酸锰(4.4m⁻？S⁻？)和HIDA锰(3.3m⁻？S⁻？)的T-⁺驰豫系数在0.5-5mm范围内几乎不变。在人血浆中，随着这些锰螯合物浓度的降低，其驰豫系数增大，提示存在与血清白蛋白结合的游离的Mn2⁺。与四氯化锰₂相比，HIDA和柠檬酸锰具有更好的收缩性能。大鼠静脉注射100mM柠檬酸锰或HIDA锰(8.3mmolKgMin⁻⁻)后，仅有微小的变化，即使在打破血脑屏障后，仍保持恒定的心率、动脉压和交感神经活动。柠檬酸锰和HIDA锰不能穿过完整的血脑屏障，出现在脑脊液中，然后通过室管膜层扩散到脑实质。在视上核内可检测到高渗刺激引起的反应。因此，柠檬酸锰和HIDA锰似乎是维持实验动物生命状态的较好选择，它们可能改善下丘脑和丘脑小核团的锰增强MRI的重复性。
In this study we investigated two manganese chelates in order to improve the image enhancement of manganese-enhanced MRI and decrease the toxicity of free manganese ions. Since both MnCl₂ and a low-affinity chelate were associated with a slow continuous decrease of cardiac functions, we investigated intermediate-affinity chelates: manganese N-(2-hydroxyethyl)iminodiacetic acid (Mn-HIDA) and Mn-citrate. The T₁ relaxivity values for Mn-citrate (4.4 m m⁻¹ s⁻¹) and Mn-HIDA (3.3 m m⁻¹ s⁻¹) in artificial cerebrospinal fluid (CSF) were almost constant in a concentration range from 0.5 to 5 m m at 37 °C and 4.7 T. In human plasma, the relaxivity values increased when the concentrations of these Mn chelates were decreased, suggesting the presence of free Mn²⁺ bound with serum albumin. Mn-HIDA and Mn-citrate demonstrated a tendency for better contractility when employed with an isolated perfused frog heart, compared with MnCl₂. Only minimal changes were demonstrated after a venous infusion of 100 m m Mn-citrate or Mn-HIDA (8.3 µmol kg⁻¹ min⁻¹) in rats and a constant heart rate, arterial pressure and sympathetic nerve activity were maintained, even after breaking the blood-brain barrier (BBB). Mn-citrate and Mn-HIDA could not cross the intact BBB and appeared in the CSF, and then diffused into the brain parenchyma through the ependymal layer. The responses in the supraoptic nucleus induced by the hypertonic stimulation were detectable. Therefore, Mn-citrate and Mn-HIDA appear to be better choices for maintaining the vital conditions of experimental animals, and they may improve the reproducibility of manganese-enhanced MRI of the small nuclei in the hypothalamus and thalamus.