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. 2018 Jan 10;8:343. doi: 10.1038/s41598-017-18702-2

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© The Author(s) 2017

Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.

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Quantitative analysis of epertinib and lapatinib in IVMs of breast cancer by IMS. The tumor concentration and tumor-to-normal brain ratio at 4 h after oral administration of epertinib or lapatinib in IVMs of breast cancer with MDA-MB-361-luc-BR2 (BR2) (open bars) and MDA-MB-361-luc-BR3 (BR3) (filled bar) are shown in (A) and (B) (epertinib: BR2 (n = 19), BR3 (n = 8), lapatinib: BR2 (n = 25), BR3 (n = 11)). At 8 h after oral administration of epertinib or lapatinib in BR3 IVM, the tumor concentration and tumor-to-normal brain ratio are shown in (C) and (D) (epertinib: n = 15, lapatinib: n = 12). The results of statistical analysis (*P < 0.05, **P < 0.01, ***P < 0.001, epertinib versus lapatinib, Welch’s t-test) are presented in (A–D). Mice (n = 6) were sacrificed at 4 h after administration epertinib or lapatinib. Each point represents fluorescence intensity for each lesion of brain metastases (n = 20) of 6 mice and those for areas of normal brain (n = 18) and choroid plexus (n = 18), (3 points randomly selected for each mouse), (E). Each point shows staining intensity of HER2 immunohistochemistry (n = 19), (F) (n.s.: not significant).