Assessing tumor vascularization as a potential biomarker of imatinib resistance in gastrointestinal stromal tumors by dynamic contrast-enhanced magnetic resonance imaging

Immunodeficient mice (n = 8 for each cell line) were grafted with imatinib-sensitive (GIST882 and GIST-T1) and imatinib-resistant (GIST430) human cell lines. Dynamic contrast-enhanced MRI (DCE-MRI) was performed on GIST xenografts to quantify tumor vessel permeability (K (trans)) and vascular volume fraction (v (p)). Microvessel density (MVD), permeability (mean dextran density, MDD), and angiogenic markers were evaluated by immunofluorescence and western blot assays.

Most metastatic gastrointestinal stromal tumors (GISTs) develop resistance to the first-line imatinib treatment. Recently, increased vessel density and angiogenic markers were reported in GISTs with a poor prognosis, suggesting that angiogenesis is implicated in GIST tumor progression and resistance. The purpose of this study was to investigate the relationship between tumor vasculature and imatinib resistance in different GIST mouse models using a noninvasive magnetic resonance imaging (MRI) functional approach.