Dynamic MR Imaging, Biodistribution and Pharmacokinetics of Polymer Shelled Microbubbles Containing Spion

Abstract

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.

Performances of a Pristine Graphene–Microbubble Hybrid Construct as Dual Imaging Contrast Agent and Assessment of Its Biodistribution by Photoacoustic Imaging

“…Figure highlights that for both the tested mice, G/PVA–PEGDA2000 MBs mainly accumulate in the liver and spleen and, in minor extent, in kidneys and lungs (see Figure S9 in the Supporting Information highlighting the anatomy of the mouse in B‐mode rendering), and result in an enhancement of the PA signal in the full body scanned volume (see Table 4 ). The observed biodistribution is in agreement with other works investigating PVA‐based MBs, not bearing graphene, as multimodal contrast agents …”

Cellular Uptake of Plain and SPION-Modified Microbubbles for Potential Use in Molecular Imaging

“…using histopathology. 4 There is an interest for in vitro adhesion and absorption profiles and mechanism of internalization for particles smaller than 0.5 μm. In our case we analyzed the uptake of micron-size bubbles with an average diameter of 3.5 μm, which are internalized by macrophages, professional phagocytic cells, but not by the endothelial cells.…”

“… 9 , 47 The different conjugations of SPIONs to plain MBs, as well as the physical, magnetic, and US-imaging properties of these MBs were recently reported. 7 , 22 , 23 , 28 , 29 , 31 , 32 , 49 , 54 The in vitro T 2 *-relaxivity, biodistribution, and in vivo pharmacokinetics of one of these MBs were evaluated using histology and MRI, 4 and just recently a study by Sciallero et al . fully characterizing the US and MR imaging properties of these bubbles was published.…”

Novel Magnetic Elastic Phase-Change Nanodroplets as Dual Mode Contrast Agent for Ultrasound and Magnetic Resonance Imaging

“…In MRI, contrast enhancement occurs due to the shortening of longitudinal (T1) and transverse (T2) relaxation times. Gadolinium-based contrast agents are currently approved for the T1-weighted positive contrast effect, i.e., an increase in image intensity in regions of contrast uptake, and superparamagnetic iron oxide nanoparticles (SPIONs) for the T2-weighted negative contrast effect, i.e., a decrease in signal intensity upon contrast administration [ 11 ].…”