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Fig. 3 | Breast Cancer Research

Fig. 3

From: Heterogeneous drug penetrance of veliparib and carboplatin measured in triple negative breast tumors

Fig. 3

a Concentrations veliparib (20 mg/kg and 60 mg/kg three times daily) quantified using LC-MS in plasma, in the three xenograft triple negative breast cancer (TNBC) cell lines and in liver tissues at the time of killing, 3 h post dose. b Correlation between veliparib plasma and tumor concentrations at the time of killing, 3 h post dose. c Difference in veliparib concentrations among the TNBC xenografts. d Correlation between total carboplatin concentrations in plasma (AUC as determined by NONMEM; see Additional file 1: Table S1) and platinum adduct formation determined by ICP-MS in the TNBC xenografts at the time of killing, 3 h post dose. e Correlation between veliparib penetration and platinum adduct formation in the TNBC xenografts at the time of killing, 3 h post dose. f Comparison of heterogeneity in the distribution of veliparib assessed by matrix-assisted laser desorption/ionization (MALDI) in the tumor region and muscle tissue using the relative standard deviation in pixel intensity as the measurement of spatial heterogeneity. g Comparison of heterogeneity in the distribution of veliparib assessed by MALDI after low dose (20 mg/kg) and high dose (60 mg/kg) veliparib administration using the relative standard deviation in pixel intensity in the whole tumor region as the measurement of spatial heterogeneity. h Comparison of the spatial distribution of veliparib assessed by MALDI in necrotic versus non necrotic regions. In this analysis, image intensity was standardized over the tumor/muscle ratio to normalize to variability in doses and pharmacokinetics. Data are shown per dose level (circle = 20 mg/kg, triangle = 60 mg/kg dose) and per individual or cell source. The black line is either the median (a) or the linear correlation (b, d, e). The R 2 value when comparing concentrations is provided. AUC area under the concentration-time curve, RSD relative standard deviation

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