Sonographic evaluation of orthotopic bladder tumors in mice treated with TNP-470, an angiogenic inhibitor

Abstract

The purpose of this study was to determine the feasibility of using transabdominal ultrasonography (US) to monitor tumor growth and response to therapy in a mouse model of orthotopic bladder carcinoma. Human bladder carcinoma cell suspensions were injected into the bladders of 18 SCID mice, allowed to grow for 3 weeks, and monitored weekly with gray-scale US. After 23 days, five animals were treated with TNP-470, an angiogenic inhibitor, and five control animals were treated with saline solution. US images were evaluated for tumor location, size, and neovascularity. All untreated animals (n = 8) were imaged and sacrificed at 25 days. Eight of the treated animals were imaged and sacrificed after 14 days of treatment. US findings for both groups were compared with autopsy findings. While saline-treated tumors continued to grow, the growth of TNP-470-treated tumors was arrested within 7 days of therapy (P < .02). Tumors as small as 1.5 mm were identified prospectively with US. US volume estimates correlated well with autopsy volume measurements (r2 = 1.0, P < .0001). Although tumor neovascularity was identified in every animal, the pattern of neovascularity did not correlate with tumor volume or therapy. US can provide accurate intermediate end points for monitoring experimental intraabdominal tumor growth and response to therapy in the mouse model.