Iron Oxide Nanoparticles For Imaging Research Articles

Ultrasonic computed tomography imaging of iron oxide nanoparticles

Iron oxide nanoparticles (IONPs) are becoming increasingly used and intensively investigated in the field of medical imaging. They are currently FDA approved for magnetic resonance imaging (MRI), and it would be highly desirable to visualize them by ultrasound as well. Previous reports using the conventional ultrasound B-scan (pulse-echo) imaging technique have shown very limited detectability of these particles. The aim of this study is to explore the feasibility of imaging IONPs using the through-transmission ultrasound methodology and demonstrate their detectability using ultrasonic computed tomography (UCT). Commercially available IONPs were acoustically analysed to quantify their effect on the speed of sound (SOS) and acoustic attenuation as a function of concentration. Next, through-transmission projection and UCT imaging were performed on a breast mimicking phantom and on an ex vivo tissue model, to which IONPs were injected. Finally, an MRI scan was performed to verify that the same particles examined in the ultrasound experiment can be imaged by magnetic resonance, using the same clinically relevant concentrations. The results have shown a consistent concentration dependent speed of sound increase (1.86 rise per 100 µg · ml−1 IONPs). Imaging based on this property has shown a substantial contrast-to-noise ratio improvement (up to 5 fold, p < 0.01). The SOS-related effect generated a well discernible image contrast and allowed the detection of the particles existence and location, in both raster-scan projection and UCT imaging. Conversely, no significant change in the acoustic attenuation coefficient was noted. Based on these findings, it is concluded that IONPs can be used as an effective SOS-based contrast agent, potentially useful for ultrasonic breast imaging. Furthermore, the particle offers the capacity of significantly enhancing diagnosis accuracy using multimodal MRI-ultrasound imaging capabilities.

Polyaspartamide-based graft copolymers encapsulating iron oxide nanoparticles for imaging and fluorescence labelling of immune cells.

Iron oxide nanoparticles (NPs) were encapsulated with polyaspartamide-based graft copolymers to bind and track the immune cells as imaging probes. Mono-disperse iron oxide NPs with a mean diameter of 10.7 nm were synthesized by the thermal decomposition method, and their shape and distribution were measured by electrophoretic light scattering and transmission electron microscopy. To enhance their biocompatibility, interfacial and hydrodynamic stability, and fluorescence detection, biodegradable polysuccinimide (PSI) grafted with several functional groups of octadecylamine (C18), ethanolamine (EA), ethylenediamine (EDA), 4-(N-maleimidomethyl) cyclohexane carboxylic acid N-hydroxysuccinimide ester (SMCC), and fluorescein isothiocyanate (FITC) was coated on the iron oxide NPs. The structure of the C18/EA/SMCC/FITC-g-PSI copolymer was confirmed using 1H-NMR and FTIR spectroscopy, and its cell binding ability was investigated by flow cytometry and confocal laser scanning microscopy. The synthesized C18/EA/SMCC/FITC-g-PSI copolymer showed an excellent binding affinity to CD4+ T cells, and was highly biocompatible as the cell viability at the highest polymer concentration of 0.4 mg mL-1 was greater than 85 and 75% after 24 and 48 h, respectively, from MTT assay.

Monoclonal antibody-conjugated superparamagnetic iron oxide nanoparticles for imaging of epidermal growth factor receptor-targeted cells and gliomas.

The objective of this study was to successfully synthesize epidermal growth factor receptor monoclonal antibody-conjugated superparamagnetic iron oxide nanoparticles (EGFRmAb-SPIONs) and explore their biocompatibility and potential applications as a targeted magnetic resonance imaging (MRI) contrast agent for the EGFR-specific detection of brain glioma in vivo. After conjugation of EGFRmAb with SPIONs, the magnetic characteristics of EGFRmAb-SPIONs were investigated. Thereafter, the targeting abilities of EGFRmAb-SPIONs with MRI were qualitatively and quantitatively assessed in EGFR-positive C6 glioma cells in vitro and in a Wistar rat model bearing C6 glioma in vivo. Furthermore, the preliminary biocompatibility and toxicity of EGFRmAb-SPIONs were evaluated in normal rats through hematology assays and histopathologic analyses. Statistical analysis was performed using one-way analysis of variance and Student t-test, with a significance level of p < .05. From the results of EGFRmAb-SPION characterizations, the average particle size was 10.21 nm and the hydrodynamic diameter was 161.5 ± 2.12 nm. The saturation magnetization was 55 emu/g·Fe, and T2 relaxivity was 92.73 s-1mM-1 in distilled water. The preferential accumulation of the EGFRmAb-SPIONs within glioma and subsequent MRI contrast enhancement were demonstrated both in vitro in C6 cells and in vivo in rats bearing C6 glioma. After intravenous administration of EGFRmAb-SPIONs, T2-weighted MRI of the rat model with brain glioma exhibited an apparent hypointense region within glioma from 2 to 48 hours. The maximal image contrast was reached at 24 hours, where the signal intensity decreased and the R2 value increased by 30% compared to baseline. However, T2-weighted imaging of the rat model administered with SPIONs showed no visible signal changes within the tumor over the same time period. Moreover, no evident toxicities in vitro and in vivo with EGFRmAb-SPIONs were clearly identified based on the laboratory examinations. EGFRmAb-SPIONs could potentially be employed as a targeted contrast agent in the molecule-specific diagnosis of brain glioma in MRI.

The diagnostic value of iron oxide nanoparticles for imaging of myocardial inflammation--quo vadis?

Cardiovascular magnetic resonance (CMR) is an integral part in the diagnostic work-up of cardiac inflammatory diseases. In this context, superparamagnetic iron oxide-based contrast agents can provide additional diagnostic information regarding the assessment of myocardial infarction and myocarditis. After intravenous administration, these nanoparticles are taken up by activated monocytes and macrophages, which predominantly accumulate in regions associated with inflammation as was successfully shown in recent preclinical studies. Furthermore, first clinical studies with a new iron oxide-complex that was clinically approved for the treatment of iron deficiency anaemia recently demonstrated a superior diagnostic value of iron oxide nanoparticles compared to gadolinium-based compounds for imaging of myocardial inflammation in patients with acute myocardial infarction. In this article, we outline the basic features of superparamagnetic iron oxide-based contrast agents and review recent studies using such nanoparticles for cardiac imaging in case of acute myocardial infarction as well as acute myocarditis. Moreover, we highlight the translational potential of these agents and possible research applications with regard to imaging and therapy.

Functionalizing silica‐coated iron oxide nanoparticles for imaging and targeted cancer therapeutics (780.3)

This project focuses on the surface modification of silica‐coated superparamagnetic iron oxide NPs to achieve tissue specific drug delivery to pancreatic tumors. The treatment of pancreatic cancer remains a challenge in the biomedical community. Over half of cases are diagnosed after the cancer has spread to other tissues, and in these cases the 5‐year survival rate is 2%. The non‐specific nature of currently available chemotherapies has spurred interest in developing vehicles to deliver potent therapies specifically to tumors. Nanoparticles (NPs) present an ideal vehicle due to their high surface area, small size, and low toxicity. Recent work explored the conjugation of NPs to a targeting moiety: monoclonal antibody CHO 31.1, which recognizes gpA33, a membrane glycoprotein overexpressed in 50% of pancreatic cancers and 95% of colorectal cancers. Building on existing methods, the antibody was attached to the silica surface of the NPs via a polyethylene glycol (PEG) linker. In vitro techniques were also developed to quantify NP detection using magnetic resonance imaging (MRI). Attachment of multiple moieties was explored using orthogonal surface chemistries. Cellular internalization was determined using confocal microscopy. Moving forward these novel nanoparticles will be further characterized for morphology, size and zeta potential, and for their utility as contrast agents for tracking in vivo.Grant Funding Source: Supported by NIH grant #1R15CA156393‐01A1

Abstract C291: Targeting SDF-1 (CXCL12) pathway to inhibit the recurrence of breast cancer brain metastases after whole-brain irradiation.

Abstract The presence of tumor-associated macrophages (TAMs) in tumors strongly correlates with poor outcome. At least one lineage of TAMs originates from the peripheral bone marrow-derived mononuclear cells. We have previously reported that bone marrow-derived CD11b+ myeloid cells contribute to tumor regrowth after irradiation by homing to the irradiated site, where they aid in restoring tumor vasculature. We have also shown that inhibiting the recruitment of CD11b+ monocytes/macrophages by blocking the SDF-1 (CXCL12)-CXCR4 axis prevents or delays recurrence of mouse and rat glioblastoma after irradiation. We further demonstrate that TAMs in the irradiated glioblastoma could be detected in vivo by magnetic resonance (MR) imaging of iron oxide nanoparticles phagocytosed by TAMs. Radiation remains one of the major modalities for treatment of breast cancer brain metastases (BCBMs). We hypothesized that inhibition of SDF-1 mediated neovasculogenesis may be as useful for treatment of BCBMs as it is for treatment of glioblastoma. In this study, brain metastases from MDA-MB-231-BR3 cells injected through intra-carotid artery in nude mice were detected by bioluminescence imaging. SDF-1 activity was inhibited using Spiegelmer NOX-A12. Treatment with NOX-A12 began immediately after irradiation, and continued every second day until the end of the experiment. We show that combination of NOX-A12 with 12Gy resulted in marked delay of metastatic regrowth after irradiation compared to 12Gy alone and a doubling of the survival time of the mice. Detection of TAMs using MR imaging of iron oxide nanoparticles is under way. Citation Information: Mol Cancer Ther 2013;12(11 Suppl):C291. Citation Format: Sophia Chernikova, G-One Ahn, Shie-Chau Liu, Jason Stafford, J. Martin Brown. Targeting SDF-1 (CXCL12) pathway to inhibit the recurrence of breast cancer brain metastases after whole-brain irradiation. [abstract]. In: Proceedings of the AACR-NCI-EORTC International Conference: Molecular Targets and Cancer Therapeutics; 2013 Oct 19-23; Boston, MA. Philadelphia (PA): AACR; Mol Cancer Ther 2013;12(11 Suppl):Abstract nr C291.

Positive contrast imaging of iron oxide nanoparticles with susceptibility‐weighted imaging

Superparamagnetic iron oxide particles can be utilized to label cells for immune cell and stem cell therapy. The labeled cells cause significant field distortions induced in their vicinity, which can be detected with magnetic resonance imaging (MRI). In conventional imaging, the signal voids arising from the field distortions lead to negative contrast, which is not desirable, as detection of the cells can be masked by native low signal tissue. In this work, a new method for visualizing magnetically labeled cells with positive contrast is proposed and described. The technique presented is based on the susceptibility-weighted imaging (SWI) post-processing algorithm. Phase images from gradient-echo sequences are evaluated pixel by pixel, and a mask is created with values ranging from 0 to 1, depending on the phase value of the pixel. The magnitude image is then multiplied by the mask. With an appropriate mask function, positive contrast in the vicinity of the labeled cells is created. The feasibility of this technique is proved using an agar phantom containing superparamagnetic iron oxide particles-labeled cells and an ex vivo bovine liver. The results show high potential for detecting even small labeled cell concentrations in structurally inhomogeneous tissue types.