Early therapy evaluation of intra-arterial trastuzumab injection in a human breast cancer xenograft model using multiparametric MR imaging

Purpose
To investigate the treatment efficacy of intra-arterial (IA) trastuzumab treatment using multiparametric magnetic resonance imaging (MRI) in a human breast cancer xenograft model.

Materials and methods
Human breast cancer cells (BT474) were stereotaxically injected into the brains of nude mice to obtain a xenograft model. The mice were divided into four groups and subjected to different treatments (IA treatment [IA-T], intravenous treatment [IV-T], IA saline injection [IA-S], and the sham control group). MRI was performed before and at 7 and 14 d after treatment to assess the efficacy of the treatment. The tumor volume, apparent diffusion coefficient (ADC), and dynamic contrast-enhanced (DCE) MRI parameters (Ktrans, Kep, Ve, and Vp) were measured.

Results
Tumor volumes in the IA-T group at 14 d after treatment were significantly lower than those in the IV-T group (13.1 mm3 [interquartile range 8.48–16.05] vs. 25.69 mm3 [IQR 20.39–30.29], p = 0.005), control group (IA-S, 33.83 mm3 [IQR 32.00–36.30], p<0.01), and sham control (39.71 mm3 [IQR 26.60–48.26], p <0.001). The ADC value in the IA-T group was higher than that in the control groups (IA-T, 7.62 [IQR 7.23–8.20] vs. IA-S, 6.77 [IQR 6.48–6.87], p = 0.044 and vs. sham control, 6.89 [IQR 4.93–7.48], p = 0.004). Ktrans was significantly decreased following the treatment compared to that in the control groups (p = 0.002 and p<0.001 for vs. IA-S and sham control, respectively). Tumor growth was decreased in the IV-T group compared to that in the sham control group (25.69 mm3 [IQR 20.39–30.29] vs. 39.71 mm3 [IQR 26.60–48.26], p = 0.27); there was no significant change in the MRI parameters.

Conclusion
IA treatment with trastuzumab potentially affects the early response to treatment, including decreased tumor growth and decrease of Ktrans, in a preclinical brain tumor model.