Duewell S, Wüthrich R, von Schulthess G K, Jenny H B, Muller R N, Moerker T, Fuchs W A
Department of Medical Radiology, University Hospital Zurich, Switzerland.
Invest Radiol. 1991 Jan;26(1):50-7. doi: 10.1097/00004424-199101000-00010.
The MR relaxation properties of ferrioxamine-B, a chelate of iron, were investigated in vitro and in vivo to establish the potential use of the compound as a paramagnetic contrast agent. Whereas the paramagnetic relaxivity of ferrioxamine-B is such that, compared to gadolinium-DTPA (Gd-DTPA), two to three times higher concentrations are necessary to produce the same relaxation effects, the toxicity of the iron ion should be much lower because of the availability of physiological metabolic pathways. Preliminary experiments in three dogs under invasive cardiovascular monitoring demonstrated that high-dose bolus application (0.1-0.3 mmol/kg body weight) of ferrioxamine-B leads to a precipitous blood pressure drop to almost zero, lasting for several minutes. This reaction seems most likely the result of a negative inotropic effect of ferrioxamine-B. In order to reduce these side effects ferrioxamine was modified to a nonionic derivative, PEG-ferrioxamine-B. In vivo experiments with this compound did not demonstrate any substantial change in blood pressure. Dynamic MR imaging of the kidneys and the liver was performed after bolus injection of the compound in six dogs. The results indicate that PEG-ferrioxamine-B produces effects very similar to Gd-DTPA, resulting in T1-mediated signal intensity increases in the liver and in the early stages of passage through the kidneys. During the phase of medullary concentration, T2 effects seem to dominate visualization of the renal medulla. The nonionic PEG-ferrioxamine-B derivative appears to offer an alternative to gadolinium-containing chelates as an MR contrast agent.
对铁螯合物去铁胺-B的磁共振弛豫特性进行了体外和体内研究，以确定该化合物作为顺磁性造影剂的潜在用途。尽管去铁胺-B的顺磁性弛豫率表明，与钆-DTPA（Gd-DTPA）相比，需要高两到三倍的浓度才能产生相同的弛豫效果，但由于存在生理代谢途径，铁离子的毒性应该要低得多。在三只接受侵入性心血管监测的犬身上进行的初步实验表明，大剂量推注（0.1-0.3 mmol/kg体重）去铁胺-B会导致血压急剧下降至几乎为零，并持续数分钟。这种反应很可能是去铁胺-B负性肌力作用的结果。为了减少这些副作用，将去铁胺修饰为非离子衍生物聚乙二醇-去铁胺-B。对该化合物进行的体内实验未显示血压有任何实质性变化。在六只犬体内推注该化合物后，对肾脏和肝脏进行了动态磁共振成像。结果表明，聚乙二醇-去铁胺-B产生的效果与Gd-DTPA非常相似，导致肝脏以及在通过肾脏的早期阶段T1介导的信号强度增加。在髓质浓缩阶段，T2效应似乎主导了肾髓质的显影。非离子聚乙二醇-去铁胺-B衍生物似乎可作为含钆螯合物的替代物用作磁共振造影剂。
