MR imaging of Her-2/neu protein using magnetic nanoparticles

Abstract

The aim of this study was to assess whether Her-2/neu expressing tumour cells can be detected in vitro as well as in animal tumour models with magnetic resonance imaging at 1.5 T. Magnetic nanoparticles (with relaxivities R 1, R 2 of 3.7 ± 0.4 (mM s)(-1), 277 ± 32 (mM s)(-1) at 21 °C, respectively) coupled to anti-Her-2/neu antibodies or gamma globulin IgG (high or non-affinity probe, respectively) were used. After incubation of Her-2/neu expressing cells (SKBR3) with high or non-affinity probes (20 min), values of R 1 = 0.34 ± 0.02 (mM s)(-1) and R 2 = 63.02 ± 30 (mM s)(-1) were obtained. Electron microscopy and atomic absorption spectrometry examinations verified the presence of relatively high iron levels in cells incubated with the high affinity probe compared to controls. For in vivo MRI, high or non-affinity probes (≈1.7 mg Fe/animal) were injected into the tail vein of mice (n = 16) bearing SKBR3 tumours. A distinct decrease in the normalized MR signal ratio between tumour and reference area (approximately -17 ± 2%) after application of the high affinity probe was observed. In conclusion, in vivo detection of Her-2/neu expressing tumours is feasible in a clinical MR scanner by using immunoconjugated magnetic nanoparticles.