Albumin-based nanoparticles as contrast medium for MRI: vascular imaging, tissue and cell interactions, and pharmacokinetics of second-generation nanoparticles

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