Magnetic resonance-imaging of the effect of targeted antiangiogenic gene delivery in a melanoma tumour model.

Abstract

We investigated the effect of targeted gene therapy to melanoma tumours (M21) by MR-imaging. M21 and M21-L tumours were grown to a size of 850 mm(3). M21 and M21-L tumours were intravenously treated with an αvβ3-integrin-ligand-coupled nanoparticle (RGDNP)/RAF(-) complex five times every 72 hours. MRI was performed at set time intervals 24h and 72h after the i.v. injection of the complex. The MRI protocol was T1-wt-SE±CM, T2-wt-FSE, DCE-MRI, Diffusion-wt-STEAM-sequence, T2-time obtained on a 1.5-T-GE-MRI device. The size of the treated M21 tumours kept nearly constant during the treatment phase (847.8±31.4 mm(3) versus 904.8±44.4 mm(3)). The SNR value (T2-weighted images) of the tumours was 36.7±0.6 and dropped down to 30.6±1.9 (p=0.004). At the beginning the SNR value (T1-weighted images) of the tumours after contrast medium application was 42.3±1.9 and dropped down to 28.5±3.0 (p<0.001). In the treatment group the diffusion coefficient increased significantly under therapy (0.54±0.01x10(-3) mm(2)/s versus 0.67±0.04x10(-3) mm(2)/s). The DCE-MRI showed a reduction of the slope and of the Akep of 67.8±4.3 % respectively 64.8±3.3 % compared to baseline. Targeted gene delivery therapy induces significant changes in MR-imaging. MRI showed a significant reduction of contrast medium uptake parameters and increase of the diffusion coefficient of the tumours. • Treatment with targeted gene-delivery therapy can be monitored by MR imaging • DCE and diffusion-weighted imaging are appropriate methods for monitoring this therapy • Functional changes are significant prior to any morphological changes.