Okon E, Pouliquen D, Okon P, Kovaleva Z V, Stepanova T P, Lavit S G, Kudryavtsev B N, Jallet P
Laboratoire de Biophysique, Faculté de Médecine, Angers, France.
Lab Invest. 1994 Dec;71(6):895-903.
Superparamagnetic iron oxide particles represent a new class of contrast agents that increase the detectability of hepatic and splenic tumors by magnetic resonance imaging (MRI). Magnetite dextran nanoparticles, a preparation with a small mean particle diameter in solution and null zêta potential present high safety margin and efficacy. The purpose of this investigation was to define the main steps of the metabolism of the iron oxide crystals.
Rats were intravenously administered a single small dose of 59Fe-labeled MD3 (3 mg Fe/kg), and the biodistribution of 59Fe was investigated in the different organs from 2 hours to 25 days postinjection. Magnetic susceptibility studies were conducted in parallel to light microscopy and immunohistochemistry from day 1 to day 14 after administration.
Most of the dose accumulated in the carcass (45%), liver (7%), and spleen (7%) in the first 2 hours. In the spleen, a continuously iron uptake was observed up to 48 hours (44%), then decreased to 25 days (22%). The splenic magnetic susceptibility dropped sharply during the first days and then more slightly until day 14. In the liver and blood, the 59Fe-level decreased at 24 hours and then increased until day 25 (11% and 27%, respectively). Histochemistry features essentially confirmed the radiotracer data and showed that iron oxide cores were accumulated into the Kupffer cells and the macrophages of the splenic marginal zone. With time, the number of the granules was decreased whereas the fine iron granules appeared in the cytoplasm. Immunopositive staining for ferritin was markedly increased in the liver hepatocytes to 3 days after injection, and in the splenic marginal zone macrophages to 14 days after injection.
The data point to the early biodegradation of the iron oxide crystals. MD3 thus appear as an interesting biodegradable new contrast agent first devoted to magnetic resonance imaging of liver and spleen diseases that could be further extended to heart, kidneys, and other organs.
超顺磁性氧化铁颗粒是一类新型造影剂，可通过磁共振成像（MRI）提高肝脏和脾脏肿瘤的可检测性。葡聚糖磁铁矿纳米颗粒是一种在溶液中平均粒径小且ζ电位为零的制剂，具有很高的安全边际和疗效。本研究的目的是确定氧化铁晶体代谢的主要步骤。
给大鼠静脉注射单次小剂量的59Fe标记的MD3（3mg铁/千克），并在注射后2小时至25天研究不同器官中59Fe的生物分布。在给药后第1天至第14天，并行进行磁化率研究以及光学显微镜和免疫组织化学研究。
在最初2小时内，大部分剂量积聚在尸体（45%）、肝脏（7%）和脾脏（7%）中。在脾脏中，观察到持续的铁摄取直至48小时（44%），然后下降至25天（22%）。脾脏磁化率在最初几天急剧下降，然后直到第14天下降较为缓慢。在肝脏和血液中，59Fe水平在24小时时下降，然后增加直至第25天（分别为11%和27%）。组织化学特征基本证实了放射性示踪剂数据，并表明氧化铁核心积聚在枯否细胞和脾脏边缘区的巨噬细胞中。随着时间的推移，颗粒数量减少，而细铁颗粒出现在细胞质中。注射后3天，肝脏肝细胞中铁蛋白的免疫阳性染色显著增加，注射后14天，脾脏边缘区巨噬细胞中铁蛋白的免疫阳性染色显著增加。
数据表明氧化铁晶体早期发生生物降解。因此，MD3似乎是一种有趣的可生物降解新型造影剂，最初用于肝脏和脾脏疾病的磁共振成像，可能会进一步扩展到心脏、肾脏和其他器官。
