Alves F Caseiro, Donato Paulo, Sherry A Dean, Zaheer Atif, Zhang Shanrong, Lubag Angelo Josue M, Merritt Matthew E, Lenkinski Robert E, Frangioni John V, Neves Maria, Prata M Isabel M, Santos A C, de Lima João J P, Geraldes Carlos F G C
Department of Radiology, Faculty of Medicine and Hospital Service of Imageology, University of Coimbra, Coimbra, Portugal.
Invest Radiol. 2003 Dec;38(12):750-60. doi: 10.1097/01.rli.0000084891.15996.0f.
GdDOTP5- is a highly charged, bone-seeking paramagnetic complex that could potentially detect bone lesions by magnetic resonance imaging (MRI). To date, its pharmacokinetics, effects on organ relaxivity, and interaction with hydroxyapatite (HA) has not been described.
Liver, kidney, and bone MRI images were obtained on male white rabbits after the administration of GdDOTP5- or a gold standard MRI contrast agent, GdDTPA2-. Parallel in vitro experiments quantified the effect of HA binding on GdDOTP5- -induced changes in relaxivity.
The 2 compounds showed similar MRI enhancements in visceral tissues, but no enhancement of bone was evident with GdDOTP5- despite confirmation of bone and HA binding of the radioactive 153SmDOTP5- and 111InDOTP5- derivatives. In vitro experiments demonstrated that GdDOTP5--induced changes in relaxivity were silenced upon HA binding but could be recovered by acid elution of the complex.
HA binding assays revealed that GdDOTP5- is essentially MR silent when bound to bone, likely because of the exclusion of all outer sphere water molecules from the surface of the complex. These data suggest a novel strategy for creating highly sensitive, switchable MRI contrast agents.
钆喷替酸葡甲胺（GdDOTP5-）是一种带高电荷、亲骨的顺磁性复合物，有可能通过磁共振成像（MRI）检测骨病变。迄今为止，其药代动力学、对器官弛豫率的影响以及与羟基磷灰石（HA）的相互作用尚未见报道。
给雄性白兔注射GdDOTP5-或金标准MRI造影剂钆二乙三胺五乙酸（GdDTPA2-）后，获取肝脏、肾脏和骨骼的MRI图像。同时进行体外实验，量化HA结合对GdDOTP5-诱导的弛豫率变化的影响。
这两种化合物在内脏组织中显示出相似的MRI增强效果，但GdDOTP5-对骨骼无增强作用，尽管已证实放射性153SmDOTP5-和111InDOTP5-衍生物与骨骼和HA结合。体外实验表明，HA结合后GdDOTP5-诱导的弛豫率变化消失，但通过复合物的酸洗脱可恢复。
HA结合试验表明，GdDOTP5-与骨结合时基本无MR信号，可能是因为复合物表面所有外层水分子被排除。这些数据提示了一种创建高灵敏度、可切换MRI造影剂的新策略。
