DYNAMIC MR IMAGING, BIODISTRIBUTION AND PHARMACOKINETICS OF POLYMER SHELLED MICROBUBBLES CONTAINING SPION

• Published in: Nano : brief reports and reviews Vol. 9; no. 6; p. 1450069
• Main Authors: BARREFELT, ÅSA, PARADOSSI, GAIO, ASEM, HEBA, MARGHERITELLI, SILVIA, SAGHAFIAN, MARYAM, ODDO, LETIZIA, MUHAMMED, MAMOUN, ASPELIN, PETER, HASSAN, MOUSTAPHA, BRISMAR, TORKEL B.
• Format: Journal Article
• Language: English
• Published: Singapore World Scientific Publishing Company 01.08.2014; World Scientific; World Scientific Publishing Co. Pte., Ltd
• Subjects: biodistribution; Condensed matter: electronic structure, electrical, magnetic, and optical properties; Construction standards; Contrast agents; Diagnostic systems; dynamic MR imaging; Exact sciences and technology; Half-life; Imaging; Iron oxides; Liver; Lungs; Macrophages; Magnetic properties and materials; Magnetic resonance imaging; Mathematical models; Medical imaging; microbubbles; Nanoparticles; Nanostructure; NMR; Nuclear magnetic resonance; Organs; Pharmacokinetics; Pharmacology; Physics; Pigments; Rats; Small particles and nanoscale materials; SPION; Spleen; Studies of specific magnetic materials; superparamagnetic iron oxide nanoparticles; Time measurement; biodistribution; microbubbles; Magnetic resonance imaging; dynamic MR imaging; superparamagnetic iron oxide nanoparticles; pharmacokinetics; SPION; Morphological changes; Iron oxide; NMR imaging; Magnetic nanomaterial; Macrophages; Agarose; super-paramagnetic iron oxide nanoparticles; Nanoparticles; Relaxation; Magnetic particles; Imaging; Polymers
• DOI: 10.1142/S1793292014500696
• ISSN: 1793-2920

Magnetic Resonance Imaging (MRI) is a noninvasive diagnostic method that provides information on morphological and physiological changes of the internal organs over time. Imaging and measurements can be repeated on the same subject, thereby reducing inter-individual variability effects and hence the number of subjects required. A potential MRI contrast agent consisting of microbubbles embedded with superparamagnetic iron oxide nanoparticles (SPION) in the shell (SPION MBs) was injected intravenously into rats to determine their biodistribution and pharmacokinetics using MR imaging. Agarose phantoms containing SPION MBs were scanned using 3 T MRI to construct a standard curve. Rats were injected with SPION MBs, free SPION or plain MBs and scanned dynamically at 3 T using a clinical MR scanner. The relaxation rate (R2*) was studied over time as a measure of the iron oxide concentrations to enable calculation of the pharmacokinetic parameters. The kinetics of SPION MBs in the liver was fitted to a one-compartment model. Furthermore, the biological fate of SPION MBs was examined via a histological survey of tissue samples using Perls' Prussian blue staining and immunohistochemistry (IHC). 1.2 h after injection of SPION MBs, T2* of the liver had decreased to its minimum. The elimination half-life of SPION MBs was 598.2 ± 97.3 h, while the half-life for SPION was 222.6 ± 26.4 h. Moreover, our study showed that SPION MBs were taken up by the macrophages in the lungs, spleen and liver. MBs labeled with SPION can be used for MR imaging. Moreover, MRI is a reliable and noninvasive tool that can be utilized in pharmacokinetic investigations of future contrast agents using SPION MBs and SPION in the rat. Biodistribution and pharmacokinetics of polymer shelled microbubbles (MBs), embedded with superparamagnetic iron oxide nanoparticles (SPION) in the shell, were determined in rats using dynamic Magnetic Resonance (MR) imaging. The histological survey of tissue samples showed that SPION MBs were taken up by macrophages in the lungs, spleen and liver. The elimination half-life of SPION MBs was longer than that of SPION. This study shows that MRI is a reliable and non-invasive method for pharmacokinetic calculations.