Nový Zbynĕk, Mandíková Jana, Trejtnar Frantisek
Charles University in Prague, Faculty of Pharmacy, Department of Pharmacology and Toxicology, Hradec Králové, Czech Republic.
Ceska Slov Farm. 2011 Feb;60(1):7-10.
Mercaptoacetyltriglycine (MAG3) and dimercaptosuccinic acid (DMSA) labelled with technetium-99m belongs to standard renal radiodiagnostics. However, the renal transport mechanisms responsible for their high renal uptake have not been fully explained. In addition, no in vitro experimental study comparing the renal uptake of these radiopharmaceuticals at the cellular level has not been performed. The investigation compared the 99mTc-MAG3 and 99mTc-DMSA renal uptake using primary rat renal cells and evaluated contribution of active and passive transport processes to the renal accumulation. The renal cells were isolated from the rat kidneys by means of the two-phase collagenase perfusion method. The used experimental model showed to be useful tool for such type of investigation. The results documented significant quantitative and qualitative differences in the accumulation of 99mTc-DMSA and 99mTc-MAG3 in the rat isolated cells. The found experimental data indicated several times higher uptake of 99mTc-MAG3 than that found in 99mTc-DMSA. 99mTc-MAG3 cellular uptake was substantially decreased when active, energy-dependent processes were inhibited. However, 99mTc-DMSA accumulation in the renal cells demonstrated only a minor dependency on energy. These findings demonstrate a very different character of the membrane transport determining 99mTc-DMSA and 99mTc-MAG3 renal accumulation.
用99m锝标记的巯基乙酰三甘氨酸（MAG3）和二巯基丁二酸（DMSA）属于标准的肾脏放射性诊断药物。然而，导致它们肾脏摄取率高的肾脏转运机制尚未得到充分解释。此外，尚未进行过在细胞水平上比较这些放射性药物肾脏摄取情况的体外实验研究。本研究使用原代大鼠肾细胞比较了99mTc-MAG3和99mTc-DMSA的肾脏摄取情况，并评估了主动和被动转运过程对肾脏蓄积的贡献。通过两相胶原酶灌注法从大鼠肾脏中分离出肾细胞。所使用的实验模型被证明是进行此类研究的有用工具。结果表明，99mTc-DMSA和99mTc-MAG3在大鼠分离细胞中的蓄积在数量和质量上存在显著差异。实验数据表明，99mTc-MAG3的摄取量比99mTc-DMSA高出数倍。当主动的、能量依赖的过程受到抑制时，99mTc-MAG3的细胞摄取量大幅下降。然而，99mTc-DMSA在肾细胞中的蓄积仅对能量有轻微依赖性。这些发现表明，决定99mTc-DMSA和99mTc-MAG3肾脏蓄积的膜转运具有非常不同的特性。
