Innovative Drug Discovery and Nanotechnology (Track)

Vascular Disrupting Agent Combining With Thalidomide Induce More Regression Of Solid Tumor Compared To The Single Use Of Both Agents Tracked By Magnetic Resonance Imaging

Feng Chen
Department of Radiology, University Hospitals, Catholic University of Leuven, Herestraat 49, 3000 Leuven, Belgium

Abstract:

Purposes: To explore the added value of antiangiogenics to vascular disrupting agent (VDA) in improving therapeutic efficacy of cancer treatment evaluated by in vivo MRI.

Materiel and Methods: A rhabdomyosarcoma tumor was implanted in the right and left liver lobes of 33 rats, for a total of 66 tumors. All animals were randomized into 3 groups: a group treated with i.v. injected single dose of VDA, zd6126, at 50 mg/kg (n=14); a group treated with VDA combined with thalidomide which were i.p. injected of 200mg/kg at 6 time points of 1d before VDA, 1d, 2d, 3d, 6d and 10d after experiment; and a control group (n=6) injected with solvent. Animals were scanned by MRI techniques including T2-weighted (T2W), diffusion-weighted (DW) imaging and T1-weighted contrast enhanced imaging (T1CE) at 5 time points of before, 4h, 2d, 6d and 12d after treatment. Tumor volume, necrosis and residual viable rim were assessed with MRI and compared between groups after sacrifice of animals at 12d. Imaging results were finally verified by histopathology. All the measurables were statistically analyzed.

Results: The tumor volume measured on T2W images was significantly reduced in combined treated group compared to VDA and control groups (p<0.05, respectively). The apparent diffusion coefficient (ADC) value was higher in combined treated group than that in VDA and control groups since 2d after treatment indicating more necrosis induced by combined therapy. The VA combined therapy caused a significant increase of unenhanced area in the tumor compared to other two groups (p<0.05, respectively) on T1CE images, while the tumor enhanced area or residual viable rim was significantly reduced in combined treated group compared to other two groups (p<0.05, respectively). The volume of tumor necrosis confirmed by pathology was significant higher in combined group than in other groups (p<0.05, respectively) except in VDA group.

Conclusions: VDA combined with thalidomide may induce more regression of solid tumor compared to the single use of VDA or thalidomide. The therapeutic effect can be evaluated by in vivo MRI.