Imaging of Her2‐targeted magnetic nanoparticles for breast cancer detection: comparison of SQUID‐detected magnetic relaxometry and MRI

Abstract

Both magnetic relaxometry and magnetic resonance imaging (MRI) can be used to detect and locate targeted magnetic nanoparticles, non-invasively and without ionizing radiation. Magnetic relaxometry offers advantages in terms of its specificity (only nanoparticles are detected) and the linear dependence of the relaxometry signal on the number of nanoparticles present. In this study, detection of single-core iron oxide nanoparticles by Superconducting Quantum Interference Device (SQUID)-detected magnetic relaxometry and standard 4.7 T MRI are compared. The nanoparticles were conjugated to a Her2 monoclonal antibody and targeted to Her2-expressing MCF7/Her2-18 breast cancer cells); binding of the nanoparticles to the cells was assessed by magnetic relaxometry and iron assay. The same nanoparticle-labeled cells, serially diluted, were used to assess the detection limits and MR relaxivities. The detection limit of magnetic relaxometry was 125,000 nanoparticle-labeled cells at 3 cm from the SQUID sensors. T2-weighted MRI yielded a detection limit of 15,600 cells in a 150 μl volume, with r1 = 1.1 mM−1s−1 and r2 = 166 mM−1s−1. Her2-targeted nanoparticles were directly injected into xenograft MCF7/Her2-18 tumors in nude mice, and magnetic relaxometry imaging and 4.7 T MRI were performed, enabling direct comparison of the two techniques. Co-registration of relaxometry images and MRI of mice resulted in good agreement. A method for obtaining accurate quantification of microgram quantities of iron in the tumors and liver by relaxometry was also demonstrated. These results demonstrate the potential of SQUID-detected magnetic relaxometry imaging for the specific detection of breast cancer and the monitoring of magnetic nanoparticle-based therapies.

Effect of BSA Protein on the Contrast Properties of Magnetite Nanoparticles during MRI

“…This agrees with typical r 2 values of small iron oxide nanoparticles -in the order of 100 (mM s) −1 [6]. However, the difference between the r 2 of particles with and without BSA protein is too small to be applicable in biomedical applications.…”

Magnetic relaxometry as applied to sensitive cancer detection and localization

“…Previously, we showed that anti-Her2-conjugated NPs specifically bind cells expressing Her2 on the surface [11]. Furthermore, we demonstrated that the magnetic moment signal correlates to the levels of Her2 expressed at the cell surface [1]. To illustrate, Figure 5A shows the results of a 15-min incubation of anti-Her2-conjugated Ocean Nanotech SHP NPs with a series of breast cancer cell lines that express Her2 to varying degrees, with MCF7/Her218 having the highest expression, MDA-MB-231 having reduced expression and Chinese hamster ovary (CHO) cells as a negative control.…”

Magnetic hyperthermia performance of magnetite nanoparticle assemblies under different driving fields

“…Herein, exchange coupling is neglected and long-range dipolar interaction is taken into consideration. 21,22 For an ensemble of randomly distributed NPs, this energy barrier is thus revised by the mean-field approximation: 23,24 …”