Antiangiogenic Tumor Treatment: Early Noninvasive Monitoring with USPIO-enhanced MR Imaging in Mice

Purpose: To prospectively investigate steady-state blood volume measurements for early quantitative monitoring of antiangiogenic treatment with ultrasmall superparamagnetic iron oxide (USPIO)–enhanced magnetic resonance (MR) imaging. Materials and Methods: The institutional animal care committee approved all experiments. HT-1080 fibrosarcoma-bearing nude mice were injected with a thrombogenic vascular targeting agent (VTA) (11 nude mice, 20 tumors) or saline (12 nude mice, 20 tumors). USPIO-enhanced (SH U 555C) MR imaging was performed after the VTA was administered. USPIO-induced changes in tissue R2* (ΔR2*) were measured with a T2-weighted dual-echo echo-planar imaging sequence, and the vascular volume fraction (VVF) was calculated. Parametric ΔR2* maps were analyzed with respect to tumor perfusion patterns. Correlative histologic analysis was performed for grading of tissue thrombosis, and tissue perfusion was quantified with fluorescent microbeads. Unpaired Student t test and Spearman nonparametric co...