Evaluating the efficacy and microenvironment changes of HER2 + gastric cancer during HLX02 and Endostar treatment using quantitative MRI

Abstract

Background and objectivesTrastuzumab is an important targeted drug for HER2-positive gastric cancer. The treatment efficacy of a more cost-effective and accessible trastuzumab biosimilar, HLX02, was not well investigated, especially when combined with antiangiogenic treatment. In addition, the tumour microenvironment detected by functional MRI was still unclear during treatment. This study attempts to evaluate the therapeutic effect of antiangiogenic agents combined with HLX02 in a HER2-positive gastric cancer xenograft model and to detect microenvironmental changes using intravoxel incoherent motion diffusion-weighted imaging (IVIM-DWI).Materials and methodsWe subcutaneously injected MKN-45 human gastric cancer cells into BALB/C nude mice to establish a tumour model. Twenty-eight mice were divided into four groups and treated with saline (Group 1), Endostar (Group 2), trastuzumab biosimilar HLX02 (Group 3), or the combination of Endostar and HLX02 (Group 4). We then performed IVIM-DWI before and at different time points after treatment. HE, HER2, TUNEL, E-cadherin staining, and α-SMA and CD31 double-staining were used to confirm the pathological changes.ResultsGroup 4 demonstrated the smallest tumour volume at the end of treatment. The D value in Group 4 increased more dramatically, with the highest value on Day 20, compared with the other groups. Perfusion-related parameters (D* and f values) in Groups 2 and 4 increased initially and reversed after Day 10. Group 4 showed the lowest CD31 and HER2 and the highest TUNEL- and E-cadherin-positive staining rates. The D value was positively correlated with TUNEL but negatively correlated with HER2 staining. The D* and f values had positive correlations with CD31 and E-cadherin expression and the vessel maturity index.ConclusionsThe trastuzumab biosimilar drug HLX02 exhibited good treatment efficacy in HER2-positive gastric cancer, especially when combined with Endostar. IVIM-DWI can noninvasively monitor the process of vascular normalization and reflect the treatment effect early at the molecular level.