Department of Health Sciences and Technology, ETH Zurich, Zurich, Switzerland.
Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Medicine, Botnar Research Centre, University of Oxford, Old Rd, Headington, Oxford, OX3 7LD, UK.
Clin Pharmacokinet. 2024 Oct;63(10):1389-1405. doi: 10.1007/s40262-024-01421-z. Epub 2024 Oct 16.
Stable iron isotope techniques are critical for developing strategies to combat iron deficiency anemia, a leading cause of global disability. There are four primary stable iron isotope methods to assess ferrokinetics in humans. (i) The fecal recovery method applies the principles of a metabolic balance study but offers enhanced accuracy because the amount of iron isotope present in feces can be directly traced back to the labeled dose, distinguishing it from endogenous iron lost in stool from shed intestinal cells. (ii) In the plasma isotope appearance method, plasma samples are collected for several hours after oral dosing to evaluate the rate, quantity, and pattern of iron absorption. Key metrics include the time of peak isotope concentration and the area under the curve. (iii) The erythrocyte iron incorporation method measures iron bioavailability (absorption and erythrocyte iron utilization) from a whole blood sample collected 2 weeks after oral dosing. Simultaneous administration of oral and intravenous tracers allows for separate measurements of iron absorption and iron utilization. These three methods determine iron absorption by measuring tracer concentrations in feces, serum, or erythrocytes after administration of a tracer. In contrast, (iv) in iron isotope dilution, an innovative new approach, iron of natural composition acts as the tracer, diluting an ad hoc modified isotopic signature obtained via prior isotope administration and equilibration with body iron. This technique enables highly accurate long-term studies of iron absorption, loss, and gain. This review discusses the application of these kinetic methods and their potential to address important questions in hematology and iron biology.
稳定铁同位素技术对于制定策略来对抗缺铁性贫血至关重要，缺铁性贫血是全球残疾的主要原因之一。有四种主要的稳定铁同位素方法可用于评估人体的铁动力学。(i) 粪便回收法应用代谢平衡研究的原理，但提供了更高的准确性，因为粪便中存在的铁同位素数量可以直接追溯到标记剂量，与从脱落的肠细胞中丢失的内源性铁区分开来。(ii) 在血浆同位素出现方法中，在口服给药后数小时内收集血浆样本，以评估铁吸收的速度、数量和模式。关键指标包括同位素浓度峰值的时间和曲线下面积。(iii) 红细胞铁掺入法通过测量口服给药后 2 周采集的全血样本中的铁生物利用度（吸收和红细胞铁利用）。同时给予口服和静脉示踪剂可以分别测量铁吸收和铁利用。这三种方法通过测量粪便、血清或红细胞中示踪剂的浓度来确定铁吸收。相比之下，(iv) 在铁同位素稀释中，这是一种创新的新方法，天然组成的铁充当示踪剂，稀释通过先前的同位素给药和与体内铁平衡获得的特定同位素标记的特征。这项技术能够对铁吸收、损失和获得进行高度准确的长期研究。本文综述了这些动力学方法的应用及其在血液学和铁生物学中解决重要问题的潜力。
