MRI methods for evaluating the effects of tyrosine kinase inhibitor administration used to enhance chemotherapy efficiency in a breast tumor xenograft model

PURPOSE: To evaluate whether quantitative MRI parameters are sensitive to the effects of the tyrosine kinase inhibitor gefitinib and can discriminate between two different treatment protocols. MATERIALS AND METHODS: Untreated mice with BT474 breast tumor xenografts were characterized in a preliminary study. Subsequently, tumor volume, apparent diffusion coefficient (ADC), transendothelial permeability (K(ps)), and fractional plasma volume (fPV) were measured in three groups of mice receiving: 1) control vehicle for 10 days, or gefitinib as 2) a single daily dose for 10 days or 3) a 2-day pulsed dose. RESULTS: Gefitinib treatment resulted in significant tumor growth inhibition (pulsed: 439 +/- 93; daily: 404 +/- 53; control: 891 +/- 174 mm(3), P < 0.050) and lower cell density (pulsed: 0.15 +/- 0.01, daily: 0.17 +/- 0.01, control: 0.24 +/- 0.01, P < 0.050) after 9 days. Tumor ADC increased in treated groups but decreased in controls (P > 0.050). Tumor K(ps) decreased with pulsed treatment but rebounded afterwards and increased with daily treatment (P > 0.050). Tumor fPV increased in both treated groups, decreasing afterwards with pulsed treatment (P > 0.050). CONCLUSION: Quantitative MRI can provide a sensitive measure of gefitinib-induced tumor changes, potentially distinguish between treatment regimens, and may be useful for determining optimal treatment scheduling for enhancing chemotherapy delivery.