Department of Chemistry, Durham University, South Road, Durham, DH1 3LE, UK.
J Biol Inorg Chem. 2014 Feb;19(2):215-27. doi: 10.1007/s00775-013-1028-y. Epub 2013 Aug 17.
Medium molecular weight glycol chitosan conjugates have been prepared, linked by an amide bond to paramagnetic Gd(III), Ho(III) and Dy(III) macrocyclic complexes in which a trifluoromethyl reporter group is located 6.5 Å from the paramagnetic centre. The faster relaxation of the observed nucleus allows modified pulse sequences to be used with shorter acquisition times. The polydisperse materials have been characterised by gel permeation chromatography, revealing an average molecular weight on the order of 13,800 (Gd), 14,600 (Dy) and 16,200 (Ho), consistent with the presence of 8.5, 9.5 and 13 complexes, respectively. The gadolinium conjugate was prepared for both a q = 1 monoamide tricarboxylate conjugate (r1p 11.2 mM(-1) s(-1), 310 K, 1.4 T) and a q = 0 triphosphinate system, and conventional contrast-enhanced proton MRI studies at 7 T were undertaken in mice bearing an HT-29 or an HCT-116 colorectal tumour xenograft (17 μmol/kg). Enhanced contrast was observed following injection in the tail vein in tumour tissue, with uptake also evident in the liver and kidney with a tumour-to-liver ratio of 2:1 at 13 min, and large amounts in the kidney and bladder consistent with predominant renal clearance. Parallel experiments observing the (19)F resonance in the holmium conjugate complex using a surface coil did not succeed owing to its high R2 value (750 Hz, 7 T). However, the fluorine signal in the dysprosium triphosphinate chitosan conjugate [R1/R2 = 0.6 and R1 = 145 Hz (7 T)] was sharper and could be observed in vivo at -65.7 ppm, following intravenous tail vein injection of a dose of 34 μmol/kg.
已制备了中等分子量的乙二醇壳聚糖缀合物，通过酰胺键与顺磁 Gd(III)、Ho(III)和 Dy(III)大环配合物连接，其中三氟甲基报告基团位于顺磁中心 6.5 Å 处。观察到的核的更快弛豫允许使用较短的采集时间使用修改后的脉冲序列。多分散材料通过凝胶渗透色谱进行了表征，显示平均分子量约为 13800（Gd）、14600（Dy）和 16200（Ho），分别与 8.5、9.5 和 13 个配合物的存在一致。为 q = 1 单酰胺三羧酸酯缀合物（r1p 11.2 mM(-1) s(-1)，310 K，1.4 T）和 q = 0 三膦酸盐系统制备了钆缀合物，并在携带 HT-29 或 HCT-116 结直肠肿瘤异种移植物的小鼠中进行了常规对比增强质子 MRI 研究 7 T（17 μmol/kg）。在静脉内尾静脉注射后，在肿瘤组织中观察到增强的对比，在肝脏和肾脏中也观察到摄取，在 13 分钟时肿瘤与肝脏的比值为 2:1，并且在肾脏和膀胱中大量存在，与主要的肾脏清除相一致。使用表面线圈观察顺磁铥配合物复合物中（19）F 共振的平行实验由于其高 R2 值（750 Hz，7 T）而没有成功。然而，在二磷酸镝壳聚糖缀合物中，氟信号 [R1/R2 = 0.6 和 R1 = 145 Hz（7 T）] 更尖锐，并且可以在体内观察到 -65.7 ppm，静脉内尾静脉注射剂量为 34 μmol/kg。
