Evaluating treatment response using DW-MRI and DCE-MRI in trastuzumab responsive and resistant @entity1722 -overexpressing human XXXX xenografts.

@entity19 @entity5 @entity0 @entity1722
We report longitudinal diffusion-weighted magnetic resonance imaging (DW-MRI) and dynamic contrast enhanced (DCE)-MRI (7 T) studies designed to identify functional changes, prior to volume changes, in trastuzumab-sensitive and resistant @entity1722 + @entity0 xenografts. Athymic @entity19 (N = 33) were subcutaneously implanted with trastuzumab-sensitive (BT474) or trastuzumab-resistant (HR6) @entity0 cells. Tumor-bearing animals were distributed into four groups: BT474 treated and control, HR6 treated and control. DW- and DCE-MRI were conducted at baseline, day 1, and day 4; trastuzumab (10 mg/kg) or saline was administered at baseline and day 3. Animals were sacrificed on day 4 and @entity5 resected for histology. Voxel-based DW- and DCE-MRI analyses were performed to generate parametric maps of ADC, K(trans), and ve. On day 1, no differences in @entity5 size were observed between any of the groups. On day 4, significant differences in @entity5 size were observed between treated vs. control BT474, treated BT474 vs. treated HR6, and treated vs. control HR6 (P < .0001). On day 1, ve was significantly higher in the BT474 treated group compared to BT474 control (P = .002) and HR6 treated (P = .004). On day 4, ve and K(trans) were significantly higher in the treated BT474 @entity5 compared to BT474 controls (P = .0007, P = .02, respectively). A significant decrease in Ki67 staining reinforced response in the BT474 treated group compared to BT474 controls (P = .02). This work demonstrated that quantitative MRI biomarkers have the sensitivity to differentiate treatment response in @entity1722 + @entity5 prior to changes in @entity5 size.
