This multidisciplinary study examined the pharmacokinetics of nanoparticles based on albumin-DTPA-gadolinium chelates, testing the hypothesis that these nanoparticles create a stronger vessel signal than conventional gadolinium-based contrast agents and exploring if they are safe for clinical use. Nanoparticles based on human serum albumin, bearing gadolinium and designed for use in magnetic resonance imaging, were used to generate magnet resonance images (MRI) of the vascular system in rats (“blood pool imaging”). At the low nanoparticle doses used for radionuclide imaging, nanoparticle-associated metals were cleared from the blood into the liver during the first 4 h after nanoparticle application. At the higher doses required for MRI, the liver became saturated and kidney and spleen acted as additional sinks for the metals, and accounted for most processing of the nanoparticles. The multiple components of the nanoparticles were cleared independently of one another. Albumin was detected in liver, spleen, and kidneys for up to 2 days after intravenous injection. Gadolinium was retained in the liver, kidneys, and spleen in significant concentrations for much longer. Gadolinium was present as significant fractions of initial dose for longer than 2 weeks after application, and gadolinium clearance was only complete after 6 weeks. Our analysis could not account quantitatively for the full dose of gadolinium that was applied, but numerous organs were found to contain gadolinium in the collagen of their connective tissues. Multiple lines of evidence indicated intracellular processing opening the DTPA chelates and leading to gadolinium long-term storage, in particular inside lysosomes. Turnover of the stored gadolinium was found to occur in soluble form in the kidneys, the liver, and the colon for up to 3 weeks after application. Gadolinium overload poses a significant hazard due to the high toxicity of free gadolinium ions. We discuss the relevance of our findings to gadolinium-deposition diseases.

这项多学科研究检查了基于白蛋白-DTPA-ga螯合物的纳米颗粒的药代动力学，检验了这些纳米颗粒比传统的基于contrast的造影剂产生更强血管信号的假设，并探讨了它们是否可安全用于临床。基于人类血清白蛋白的纳米粒子，带有g并设计用于磁共振成像，被用于生成大鼠血管系统的磁共振图像（MRI）（“血池成像”）。在用于放射性核素成像的低纳米粒子剂量下，在纳米粒子应用后的最初4小时内，与纳米粒子相关的金属从血液中清除了进入肝脏。在进行MRI所需的更高剂量下，肝脏变得饱和，肾脏和脾脏成为金属的额外吸收体，并占了纳米颗粒的大部分加工量。纳米颗粒的多种组分彼此独立地被清除。静脉注射后长达2天在肝脏，脾脏和肾脏中检测到白蛋白。d以较高浓度保留在肝脏，肾脏和脾脏中的时间更长。application在施用后超过2周以初始剂量的显着比例存在，g的清除仅在6周后完成。我们的分析无法定量说明所用applied的全部剂量，但是发现许多器官的结缔组织胶原中都含有g。多方面的证据表明，胞内加工会打开DTPA螯合物并导致g的长期保存，特别是在溶酶体内。发现储存application的周转以可溶形式在肾脏，肝脏和结肠中发生，施用后长达3周。由于游离overload离子的高毒性，d超载构成重大危险。我们讨论了我们的发现与g沉积疾病的相关性。