Neuroradiology Unit, Sant'Andrea Hospital, Via di Grottarossa 1035, 00189, Rome, Italy.
Medical Physics Unit, Risk Management Enterprise, Bambino Gesù Children's Hospital, Rome, Italy.
CNS Drugs. 2018 Mar;32(3):229-240. doi: 10.1007/s40263-018-0500-1.
In recent years, gadolinium-based contrast agents have been associated with different types of toxicity. In particular, nephrogenic systemic fibrosis, a progressive sclerotic-myxedematous systemic disease of unknown etiology, is related to gadolinium-based contrast agent administration in patients with kidney dysfunction. More recently, evidence of magnetic resonance signal intensity changes on pre-contrast T1-weighted images after multiple gadolinium-based contrast agent administrations resulted in the hypothesis of gadolinium brain accumulation in patients with normal renal function, subsequently confirmed in pathological samples. However, there is limited current data and further investigations are necessary before drawing definite conclusions on the clinical consequences of gadolinium-based contrast agent accumulation in human tissues and particularly in the brain. Gadolinium-based contrast agent-related toxicity appears connected to molecular stability, which varies together with the pharmacokinetic properties of the compound and depends on the individual characteristics of the subject. During a lifetime, the physiological changes occurring in the human body may influence its interaction with gadolinium-based contrast agents: the integrity and developmental stage of the organs has an effect on the dynamics of gadolinium-based contrast agent distribution and excretion, thus leading to different possible mechanisms of deposition and toxicity. Therefore, the aim of this work is to discuss the pharmacokinetics and pharmacodynamics of gadolinium-based contrast agents, with a special focus on the brain, and to explore potential predominant gadolinium-based contrast agent-related toxicity in two cornerstone periods of the human life cycle: fetal/neonatal and adulthood/aged.
近年来，钆基造影剂与不同类型的毒性有关。特别是肾源性系统性纤维化，一种病因不明的进行性硬化黏液水肿性全身性疾病，与肾功能障碍患者中使用钆基造影剂有关。最近，在多次使用钆基造影剂后，预对比 T1 加权图像上的磁共振信号强度变化的证据导致了在肾功能正常的患者中存在钆脑蓄积的假设，随后在病理样本中得到证实。然而，目前的数据有限，在对人类组织（特别是大脑）中钆基造影剂蓄积的临床后果得出明确结论之前，还需要进一步研究。与钆基造影剂相关的毒性似乎与分子稳定性有关，而分子稳定性又与化合物的药代动力学特性一起变化，并取决于个体的特点。在一生中，人体发生的生理变化可能会影响其与钆基造影剂的相互作用：器官的完整性和发育阶段会影响钆基造影剂的分布和排泄动力学，从而导致不同的可能沉积和毒性机制。因此，这项工作的目的是讨论钆基造影剂的药代动力学和药效动力学，特别是在大脑方面，并探讨在人类生命周期的两个基石时期（胎儿/新生儿和成年/老年）中潜在的主要与钆基造影剂相关的毒性。
