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

Breast Cancer Research

Table 1 Veliparib concentrations by LC-MS (left) and its spatial distribution by MALDI (bottom) varies by tissue, drug dose and TNBC cell line of origin

	Tissue	Amount of tissue median (RSE)	Comparison		Method	Subjects (N)	Tissues (N)	Tissues (N) <LOD; <LOQ	Median conc. (RSE %)^a	Ion intensity tumor/muscle (RSE %);	P
a) Veliparib	Plasma	50 μL	20 mg/kg 60 mg/kg		LC-MS	9 6	9 6	1; 0 0; 0	0.19 (10) 0.86 (11)		<0.001 (Low/high dose)
	Muscle	49.9 mg (13%)	20 mg/kg 60mg/kg			5 6	5 6	2; 3 1; 1	0.12 (70) 0.47 (47)		0.882 (Muscle/plasma)*
	Liver	49.9 mg (12%)	20 mg/kg 60 mg/kg			6 6	6 6	0; 0 0; 0	0.47 (20) 1.77 (14)		<0.001 (Liver/plasma)*
	TNBC xenograft tissue	46.1 mg (8%)	20 mg/kg 60 mg/kg			12 12	19 17	8; 15 0; 1	0.12 (31) 0.36 (12)		0.322 (Tumor/plasma) 0.0038 (tumor/plasma)
			HCC70	20 mg/kg		4	6	2; 4	0.13 (43)		0.0367 (Cell source)*
			HCC70	60 mg/kg		5	9	0; 0	0.43 (16)
			MDA-MB-231	20 mg/kg		4	7	4; 6	0.01 (62)
			MDA-MB-231	60 mg/kg		4	5	0; 1	0.27 (18)
			MDA-MB-436	20 mg/kg		4	6	2; 5	0.05 (47)
			MDA-MB-436	60 mg/kg		3	3	0; 0	0.32 (26)
		12 μm section	20 mg/kg 60 mg/kg		MALDI	6 9	6 12			0.98 (16); 0.02 1.36 (19); 0.13	<0.001 (Low/high dose)
		12 μm section	Necrotic tumors Cellular tumors		MALDI	15 15	18 18			1.63 (70%) 1.01 (85%)	0.084 (ROI)*

MALDI matrix-assisted laser desorption/ionization, TBNC triple negative breast cancer, PBMC peripheral blood mononuclear cells, RSE relative standard errors, ROI region of interest, V veliparib
^aConcentration (Conc.) of veliparib and carboplatin in mg/L, carboplatin adducts in μmol/g DNA
*P value adjusted for dose

ISSN: 1465-542X