The study of vascular disrupting agent A64 combined with bevacizumab in the treatment of NSCLC using Multiple b-value DWI
Chang-Zheng Shi1, Dong Zhang2, Liang-Ping LUO3, and Yong Zhang4

1Jinan University, Guangzhou, China, People's Republic of, 2guangzhou, China, People's Republic of, 3Guangzhou, China, People's Republic of, 4GE Healthcare MR Research China, Beijing, Beijing, China, People's Republic of

Synopsis

Studies showed that vascular disrupting agents and angiogenesis inhibitors had a synergistic effect for the treatment of cancer. Few previous reports used MRI to assess the combination of anti-angiogenesis drugs in non-small cell lung cancer(NSCLC). MR multi-b value diffusion-weighted imaging can be used to monitor the treatment of tumor by anti-angiogenesis drugs. In our study , the nude mice xenograft model was used to evaluate the role of vascular disrupting agents combing angiogenesis inhibitor in NSCLC by multiple b-value diffusion weighted imaging (DWI).

Purpose

Studies showed that vascular disrupting agents and angiogenesis inhibitors had a synergistic effect for the treatment of cancer[1]. Few previous reports used MRI to assess the combination of anti-angiogenesis drugs in non-small cell lung cancer(NSCLC). MR multi-b value diffusion-weighted imaging can be used to monitor the treatment of tumor by anti-angiogenesis drugs[2]. In our study , the nude mice xenograft model was used to evaluate the role of vascular disrupting agents combing angiogenesis inhibitor in NSCLC by multiple b-value diffusion weighted imaging (DWI).

Methods

NSCLC in nude mice xenograft models were established with A549 cells. Divided the nude mice into two groups, group A was treated with vascular disrupting agent A64 jointed bevacizumab, group B was treated with A64 alone. Underwent multiple b-value DWI scanning and calculated the D values before and after treatment using introvoxel incoherent motion (IVIM) model. The difference was compared in the group and inter-group at 2h, 48h, 96h and 8d respectively, Meanwhile analysing the histological characteristic of the tumor parallely with immunohistochemical staining of ki67 and Tunel.

Results

The D values decreased significantly at 2h in both group A and B, then increased significantly at 48h and 96h , and decreased again at 8d. In group B, the D values increased less significantly than those in group A at 48h and 96h, and decreased more significantly than that of group A at 8d(Fig.1). In both group A and B, the change of positive rate of ki67 staining was not significant at 2h after treatment, and decreased to the lowest at 48h, then began to increase at 96h and 8d, and the rate increased more significantly in group B than that in group A (Fig.2). In both group A and B, the change of positive rate of Tunel staining increased slightly at 2h, and increased rapidly at 48h, then decreased gradually at 96h and 8d, Furthermore, the rate of group A at 8d was higher than that in group B (Fig.3).

Discussion and conclusion

The change of D calculated from IVIM model is related with the positive rate of ki67 and Tunel staining, and reflect the efficacy of A64 and A64 jointed bevacizumab respectively. In promoting the tumor cell apoptosis at the early period and inhibiting the tumor cell proliferation at the late period, treatment with A64 jointed bevacizumab shows better efficacy than with A64 alone.

Acknowledgements

No acknowledgement found.

References

[1]Nathan P, Zweifel M, Clinical Cancer Research, 2012.[2]Koh D M, Collins D J, et al.American Journal of Roentgenology, 2011.

Figures

Fig 1 The D map of the maximum slice in different group at 2h, 48h, 96h and 8d.

Fig 2 The staining of Ki67 in different group at 2h, 48h, 96h and 8d.

Fig 3 The staining of Tunel in different group at 2h, 48h, 96h and 8d.



Proc. Intl. Soc. Mag. Reson. Med. 24 (2016)
2647