New DCE-MRI Parameters to Quantify the Vascular Changes Induced by Sunitinib Treatment in Renal Carcinoma Tumors* *Resrach supported by Pfizer.

To develop new dynamic contrast enhanced (DCE) magnetic resonance imaging (MRI) parameters to quantify the vascular effects of different doses of the antiangiogenic drug sunitinib on renal cell carcinoma (RCC) kidney tumors in mice. Mice bearing established RCC xenograft tumors were treated with sunitinib doses of 10, 20 or 40 mg/kg/day (SU10, SU20 or SU40 respectively) or treated with vehicle only (control). New DCE parameters, contrast agent uptake to the peak (AUCtp), time to peak concentration (TTP), washout slope (Nslope) and full width half maximum (FWHM), were obtained from T1-weighted images. These parameters were quantified for tumor-bearing kidneys and normal kidneys. Treatments with SU20 and SU40 caused increased perfusion in the tumor core compared to control and SU10. Kidney tumors treated with SU20 had an almost identical pattern of contrast agent uptake rate, peak and clearance as those observed in normal kidneys. The effect of SU20 on normal kidneys was milder than that observed with SU40. Treatment with SU40 caused increased contrast agent uptake by the cortex of the normal kidneys compared to the normal kidneys in control and SU10. FWHM also provided new information about the effect of different treatment doses and showed that kidney tumors treated with SU20 have almost the same values of FWHM as the normal kidneys in control mice. The new DCE parameters, including AUCtp, Nslope and FWHM, have the potential to give a precise description of the treatment effect not only in the whole mouse kidney but also in different regions inside the kidney.