Borborema Samanta Etel Treiger, Osso João Alberto, Andrade Heitor Franco de, Nascimento Nanci do
Centro de Biotecnologia, Instituto de Pesquisas Energéticas e Nucleares, Comissão Nacional de Energia Nuclear, São Paulo, SP, Brasil.
Mem Inst Oswaldo Cruz. 2013 Aug;108(5):623-30. doi: 10.1590/0074-0276108052013014.
Pentavalent antimonials such as meglumine antimoniate (MA) are the primary treatments for leishmaniasis, a complex disease caused by protozoan parasites of the genus Leishmania . Despite over 70 years of clinical use, their mechanisms of action, toxicity and pharmacokinetics have not been fully elucidated. Radiotracer studies performed on animals have the potential to play a major role in pharmaceutical development. The aims of this study were to prepare an antimony radiotracer by neutron irradiation of MA and to determine the biodistribution of MA in healthy and Leishmania (Leishmania) infantum chagasi-infected mice. MA (Glucantime®) was neutron irradiated inside the IEA-R1 nuclear reactor, producing two radioisotopes, ¹²²Sb and ¹²⁴Sb, with high radionuclidic purity and good specific activity. This irradiated compound presented anti-leishmanial activity similar to that of non-irradiated MA in both in vitro and in vivo evaluations. In the biodistribution studies, healthy mice showed higher uptake of antimony in the liver than infected mice and elimination occurred primarily through biliary excretion, with a small proportion of the drug excreted by the kidneys. The serum kinetic curve was bi-exponential, with two compartments: the central compartment and another compartment associated with drug excretion. Radiotracers, which can be easily produced by neutron irradiation, were demonstrated to be an interesting tool for answering several questions regarding antimonial pharmacokinetics and chemotherapy.
五价锑化合物，如葡甲胺锑酸盐（MA），是治疗利什曼病的主要药物，利什曼病是一种由利什曼原虫属的原生动物寄生虫引起的复杂疾病。尽管已临床使用70多年，但其作用机制、毒性和药代动力学尚未完全阐明。在动物身上进行的放射性示踪研究有可能在药物研发中发挥重要作用。本研究的目的是通过对MA进行中子辐照制备一种锑放射性示踪剂，并确定MA在健康小鼠和感染婴儿利什曼原虫（Leishmania infantum chagasi）的小鼠体内的生物分布。MA（葡糖胺锑）在IEA-R1核反应堆内进行中子辐照，产生两种放射性同位素¹²²Sb和¹²⁴Sb，具有高放射性核素纯度和良好的比活度。在体外和体内评估中，这种辐照后的化合物表现出与未辐照MA相似的抗利什曼活性。在生物分布研究中，健康小鼠肝脏中锑的摄取量高于感染小鼠，排泄主要通过胆汁进行，少量药物通过肾脏排泄。血清动力学曲线呈双指数型，有两个房室：中央房室和另一个与药物排泄相关的房室。经证明，通过中子辐照可轻松制备的放射性示踪剂是回答有关锑药代动力学和化疗的几个问题的有趣工具。
