Evaluating treatment response using DW-MRI and DCE-MRI in trastuzumab responsive and resistant HER2-overexpressing human breast cancer xenografts

Abstract

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 HER2 + breast cancer xenografts. Athymic mice (N = 33) were subcutaneously implanted with trastuzumab-sensitive (BT474) or trastuzumab-resistant (HR6) breast cancer 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 tumors resected for histology. Voxel-based DW- and DCE-MRI analyses were performed to generate parametric maps of ADC, Ktrans, and ve. On day 1, no differences in tumor size were observed between any of the groups. On day 4, significant differences in tumor 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 Ktrans were significantly higher in the treated BT474 tumors 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 HER2 + tumors prior to changes in tumor size.

Trastuzumab improves tumor perfusion and vascular delivery of cytotoxic therapy in a murine model of HER2+ breast cancer: preliminary results

“…(We note that animals ( N = 20) utilized in the imaging study (experiment one, described below) are a subset of animals included in a previous study [33]). Nude athymic female mice ( N = 135) were subcutaneously implanted with a 0.72 mg, 60-day release, 17β-estradiol pellet (Innovative Research of America, Sarasota, FL).…”

Diffusion-Weighted Mri in the Differential Diagnosis of Brain Meningiomas

“…Согласно результатам ряда зарубежных иссле-дований, методика ДВ МРТ с построением ДВИ и вычислением ИКД может быть использована в качестве маркера прогнозирования эффективности лечения различных злокачественных опухолей [14][15][16]. Однако публикации, посвященные при-менению ДВ МРТ при менингиомах головного мозга, немногочисленны и во многом противо-речивы [17][18][19][20].…”

The Attenuation Distribution Across the Long Axis (ADLA)

“…This could be done by incorporating image feature analysis functions into commercial Picture archiving and communication system (PACS) software. By contrast, advanced quantitative imaging techniques like contrast-enhanced perfusion CT and dynamic contrast-enhanced magnetic resonance imaging (3,14–17) are complex and resource-intensive and may be difficult to use in a standardized manner across different institutions. The demand for semiquantitative biomarkers that are readily extractable from standard-of-care scans has already been made evident; in the ACRIN 6657/I-SPY trial of magnetic resonance imaging for the prediction of breast cancer response to neoadjuvant chemotherapy, for example, investigators chose a simple, semiquantitative, three-point signal enhancement ratio method over more complex pharmaco-kinetic modeling approaches, citing the need to standardize image acquisition and data processing across different system platforms at multiple institutions (18).…”