Study of diffusion-weighted magnetic resonance imaging in the evaluation of the response to AAV2-VEGF-Trap neoadjuvant treatment in a triple-negative breast cancer animal model

Abstract

Objective: Evaluation of the efficacy of adeno-associated virus 2 mediated gene transfer of vascular endothelial growth factor Trap (AAV2-VEGF-Trap) alone or combination with paclitaxel in a mouse model of triple-negative breast cancer (TNBC) using diffusion-weighted magnetic resonance imaging (DW-MRI) and in vivo fluorescence imaging.

Materials and methods: Xenografted TNBC tumors were established by subcutaneous injection of MDA-MB-231 cells into nude mice. Tumors were treated with AAV2-VEGF-Trap, paclitaxel, AAV2-VEGF-Trap combined with paclitaxel and control. A 7.0-Tesla magnetic resonance (MR) was used to obtain the apparent diffusion coefficient (ADC) values and ΔADC values. In vivo fluorescence imaging coupled with the optical imaging probe AngioSense680 EX was acquired to obtain average luminous intensity values. Immunohistochemical staining of tumor Ki-67 and vascular endothelial cell marker antigen (CD31) were used to evaluate the effects on tumor proliferation and angiogenesis.

Results: The combination of AAV2-VEGF-Trap with paclitaxel exhibited greater tumor growth inhibition compared with the other groups. The ADC values in the paclitaxel group and the AAV2-VEGF-Trap in combination with paclitaxel group were significant greater compared with the control group, and the ΔADC values of all treatment groups were significantly increased compared with the control group on the 14th day after administration. Decreased microvessel density and luminous intensity in the treatment groups that contain AAV2-VEGF-Trap were observed. Reduced proliferation activity was noted in groups that contained paclitaxel.

Conclusion: AAV2-VEGF-Trap inhibits TNBC growth though inhibiting tumor neovascularization with a single intravenous injection, and AAV2-VEGF-Trap exhibits a synergistic effect when used in combination with paclitaxel for TNBC neoadjuvant therapy. In vivo fluorescence imaging can detect the anti-angiogenesis effect of AAV2-VEGF-Trap early and noninvasively. DW-MRI can longitudinally monitor the neoadjuvant efficacy of TNBC.

Keywords: AAV2-VEGF-Trap; angiogenesis; apparent diffusion coefficient; diffusion-weighted magnetic resonance imaging; in vivo fluorescence imaging; triple-negative breast cancer; Δ ADC.