Doppler ultrasound imaging detects changes in tumor perfusion during antivascular therapy associated with vascular anatomic alterations

Noninvasive monitoring of antiangiogenic therapy was performed by serial po wer Doppler ultrasound imaging of murine tumors treated with recombinant in terleukin 12, the results of which were correlated with assessments of tumo r vascularity by microscopy, Growth of established K1735 tumors, but not of IFN-gamma -unresponsive K1735,N23 variants, was suppressed by treatment. S erial Doppler imaging of K1735 tumor vascularity during treatment revealed a progressive change from a diffuse perfusion pattern to a more punctate di stribution. Quantitative analysis of the images revealed that color-weighte d fractional average, representing overall tumor perfusion, consistently de creased in these tumors, primarily because of a decrease in fractional tumo r cross-sectional area carrying blood flow. In contrast, these parameters i ncreased in nonresponsive tumors during treatment. Confocal microscopy of t hick tumor sections revealed a reduction in the density and arborization of vessels labeled in vivo by fluorochrome-conjugated lectin with effective t reatment. Immunohistological examination of thin tumor sections confirmed t he preferential loss of small vessels with successful therapy. Similar chan ges in tumor vascular anatomy and perfusion were also observed during recom binant interleukin 12 treatment of two other responsive murine tumor types. These results indicate that power Doppler ultrasound is a sensitive, nonin vasive method for reporting functional consequences of therapy-induced vasc ular anatomical changes that can be used to serially monitor tumor perfusio n and efficacy of antivascular therapy in clinical trials.