Changes of tumor vascularity during gene therapy monitored with color Doppler US

Using contrast-enhanced color Doppler (CD) sonography, we assessed alterations of tumor blood flow induced in 25 murine Morris hepatomas transfected with a gancyclovir- (GCV-)sensitizing Herpes simplex virus thymidine kinase (HSVtk) suicide gene in combination with systemic GCV treatment and compared findings with a control tumor. CD measurements were quantified by the color pixel density (CPD) and the mean encoded flow velocity (mean color value, MCV), using computer-assisted image analysis, and compared with histologic arteriole counts. During 5 days, the tumor volume remained constant. In HSVtk-expressing tumors, the median CPD dropped from 16% at baseline to 5% on day 5 (p = 0.001), remaining constant in controls. The MCV decreased from 1.9 cm/s to 1.6 cm/s in the HSVtk-expressing tumors (p = 0.001) and rose from 1.8 cm/s to 2.0 cm/s in the controls (p = 0.002). In an accompanying histologic arteriole assay, we found no alterations attributable to treatment.