Evaluating vascular normalization in orthotopic triple negative breast cancer with metronomic chemotherapy using 3D-UTE-GRASP DCE MRI

Motivation: Metronomic chemotherapy shows promise as a cost-effective therapy for vascular normalization. However, it is unclear how to determine the optimal biological dose (OBD). Goal(s): Our goal is to use dynamic contrast-enhanced (DCE) MRI and pharmacokinetic analysis for non-invasive measurements of the heterogenous tumor treatment response toward determining the OBD. Approach: The 4T1 murine orthotopic triple negative breast cancer models were assessed longitudinally using two different dosing schemes, daily and intermittent, using cyclophosphamide. Pharmacokinetic and histological analysis (CD31, Ki67) were conducted. Results: The intermittent dosing schedule showed higher Vp, Fp, and Ktrans in all tumor regions indicating possible vascular normalization. Impact: The proposed 3D-UTE-GRASP DCE-MRI method provides a non-invasive platform to assess for optimal biological dose in metronomic chemotherapy. By accurately determining the heterogenous tumor vessel dynamical changes, this platform can be used to enhance treatment response over time.