Synthesis and characterization of HE-24.8: A polymeric contrast agent for magnetic resonance angiography
Synthesis and characterization of HE-24.8: A polymeric contrast agent for magnetic resonance angiography
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DOI：
10.1021/bc0501909
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发表时间：
2006-01-01
影响因子：
4.7
通讯作者：
Semmler, W
中科院分区：
文献类型：
--
作者：
Kiessling, F;Heilmann, M;Semmler, W
研究了基于N-（2-羟丙基）甲基丙烯酰胺共聚物与钆（HE-24.8）的复合物的水溶性聚合物造影剂的物理和生物学性质，并评估了其用于实验性磁共振（MR）血管造影的潜力。在1.5T下测定Gd-DTPA-BMA、Gd-DTPA-HSA（人血清白蛋白）和HE-24.8的弛豫率。在体外并通过分析大鼠体内长达2周的动力学和器官分布来评估HE-24.8的热稳定性和生物相容性。为了进行比较，在大鼠中进行了脑、胸部和皮下肿瘤的HE-24.8-和Gd-DTPA-HSA-增强的显微MR血管造影。HE-24.8的T-1弛豫率（21.3 +/- 1.1 mM（-1）s（-1））是Gd-DTPA-BMA的5倍（4.1 +/- 0.1 mM（-1）s（-1）），是Gd-DTPA-HSA的2倍（12.4 +/- 0.2 mM（-1）s（-1））。改变聚合物的分子量（15-46 kDa）没有显著改变T-1弛豫率。在大鼠中，分别在注射后24和168 h检测到注射剂量的20%和10%的HE-24.8。在相对快速的初始肾脏清除后，除网状内皮系统外，在任何器官中均未观察到特异性滞留。在水性环境中孵育期间，未观察到聚合物-Gd复合物中钆的可测量释放或细胞毒性。Gd-DTPA-HSA和HE-24.8对大鼠和肿瘤血管形成显示良好;然而，HE-24.8增强扫描的血管对比度较高。HE-24.8被认为是非常适合实验性MR研究的大分子造影剂。
The physical and biological properties of a water-soluble polymeric contrast agent based on a complex of N-(2-hydroxypropyl)methacrylamide copolymer with gadolinium (HE-24.8) were investigated, and its potential for experimental magnetic resonance (MR) angiography was assessed. Relaxivities of Gd-DTPA-BMA, Gd-DTPA-HSA (human serum albumin), and HE-24.8 were determined at 1.5 T. Thermic stability and biocompatibility of HE-24.8 were assessed in vitro and by analyzing kinetics and organ distribution in rats for up to 2 weeks. For comparison, HE-24.8- and Gd-DTPA-HSA-enhanced micro-MR angiographies of brain, chest, and subcutaneous tumors in rats were performed. T-1 relaxivity of HE-24.8 (21.3 +/- 1.1 mM(-1) s(-1)) was 5-fold higher than that of Gd-DTPA-BMA (4.1 +/- 0.1 mM(-1) s(-1)) and twice as high as that of Gd-DTPA-HSA (12.4 +/- 0.2 mM(-1) s(-1)). Varying the molecular weight of the polymer (15-46 kDa) did not significantly change the T-1 relaxivity. In rats, 20 and 10% of the injected dose of HE-24.8 was detected at 24 and 168 h postinjection, respectively. Upon a relatively rapid initial renal clearance, no specific retention in any organ was noted, with some exception for the reticulo-endothelial system. No measurable release of gadolinium from the polymer-Gd complex or cell toxicity was observed during its incubation in aqueous environment. Excellent display of rat and tumor vascularization was achieved with Gd-DTPA-HSA and HE-24.8; however, contrast of vessels was higher in HE-24.8-enhanced scans. HE-24.8 is considered a macromolecular contrast agent highly suited for experimental MR studies.