Nasopharyngeal carcinoma (NPC) is one of the most common malignancies of the head and neck in Southeast Asia. Chemoradiotherapy is the main treatment of choice for the NPC. Vandetanib (ZD6474), an oral small-molecule multitargeted tyrosine kinase inhibitors (TKIs), has been revealed to exhibit anti-angiogenic and anti-proliferative effects in some kinds of tumors, including NPC1. By implementing a bi-exponential fitting model with multiple b values, perfusion-related parameters such as the perfusion fraction (f) and blood pseudodiffusion coefficient (D*), and diffusion-related parameters such as the true diffusion coefficient (D), can be separately measured2,3. Therefore, the purpose of the present study was to investigate the feasibility of IVIM DWI to evaluate the early therapeutic effects of ZD6474 upon human NPC xenografts in nude mouse.24 CNE-2 human NPC mice were randomly allocated to either the control group or the ZD6474-treated group. Mice in the treated and control group were administered with ZD6474 or vehicle by oral gavage at a dose of 100 mg/kg once daily for 7 day. MRI was performed before treatment (day 0) and at 1, 3, and 7 days after treatment on a 3.0T MR scanner (GE Healthcare, Milwaukee, WI) with a custom-built-8-channel receiver coil. The IVIM DWI sequence was obtained using a single-shot EPI with 12 b-values of 0, 20, 50, 100, 150, 200, 400, 600, 800, 1200, 1600, and 2000 s/mm2 (TR/TE, 3000 ms/102.4 ms; flip angle, 90°; matrix, 64× 64; field of view, 80 × 80 mm2; section thickness, 2.4 mm; NEX, 4) (Fig. 1). All the IVIM parameter maps were generated automatically by the MADC program (Fig. 2). All the tumors were harvested and underwent histological assessment for HE, CD31, Ki-67 and terminal nucleotidyltransferase-mediated nick end labeling (TUNEL) assay. The Student’s t test or the Mann-Whitney test was used for analysis of all the ADC and IVIM parameters and all histopathological indices of the tumors between the control and treated groups.For the diffusion-related parameters, both the mean value and relative changes in ADC and D values significantly higher than those in the control group starting from day 3 (Table 1, Fig.3A and 3B). For the perfusion-related parameters, the mean D* value in the treated group was lower than that in the control group from day 3 (Table 1), while the relative change in D* value in the treated group decreased significantly compared with that in the control group within only 1 day (Fig.3C). The mean and percentage of changes in f values of the tumor were significantly decreased in the treated group compared with those in the control group after only 1day (Table 1 and Fig.3D). As show in Fig.4, a decrease in cellular density with more necrotic areas and decreased MVD scores in ZD6474-treated tumors were seen compared to those of tumors in the control group on day 7. The proliferative index Ki-67 in the treated group was significantly lower than that in the control group, while the apoptosis index was significantly higher than that in the control group, indicating an effective therapeutic response. In this preliminary study, we found perfusion-related parameters f and D*, which reflect the blood volume and velocity inside the tumors, change earlier than diffusion-related parameters ADC and D, which reflect the rate of microscopic water diffusion as a marker of cellular density or necrosis. Therefore, the present study demonstrated that IVIM DWI is sensitive to detect the ZD6474-induced changes in human NPC in nude mouse, while the D* and f parameter could allow for prediction of the early tumoral response to anti-angiogenic treatment.