Abstract 1572: Characterising the tumor vasculature in vivo in mouse models of colorectal cancer using contrast enhanced high-frequency ultrasound

Abstract

Abstract Angiogenesis is essential for tumours to grow beyond a few millimetres in size and to metastasise, making it an attractive target for both cancer imaging and therapeutic intervention. Although microvessel density (MVD) is routinely used to assess tumour vascularity in fixed tissue, few techniques are currently available for imaging and quantitating tumour vasculature parameters in vivo. High-frequency ultrasound (HFUS) allows high resolution, non-invasive longitudinal imaging of tumours in vivo. Incorporation of microbubble contrast agent into imaging protocols allows visualisation of the vasculature, determination of relative blood flow and perfusion, and the ability to directly target and quantify molecular biomarkers of disease in vivo. We have been investigating in vivo tumour blood flow and vascularity in the growth of human colorectal cancer (CRC) cell xenografts. CD1 Nu/Nu mice implanted with SW480 cell xenografts were used to investigate the relationship between tumour growth and different vascular parameters obtained by contrast enhanced (CE) HFUS. Mice were imaged at day 21 and day 27 of tumour growth using the VisualSonics Vevo 770 system. A single bolus of microbubbles was injected via a syringe driver into the tail vein during 2D CE HFUS imaging, with the wash-in data loops captured prior to 3D CE HFUS imaging, and tissue samples collected for histology and immunohistochemistry. Time intensity curves were generated post-acquisition and used to determine perfusion kinetics and vascular data. A number of strongly significant correlations were observed relating in vivo and histological tumour characteristics with relative blood flow and total vascularity. These included the size of the tumour, tumour growth and the total vascular space. This study shows that CE HFUS is a powerful qualitative and quantitative tool for the analysis of tumour angiogenesis in vivo. It provides a relatively non-invasive method to monitor tumour blood flow and vascularity in longitudinal studies thus allowing effects on angiogenesis due to therapeutic intervention to be monitored. We are currently developing this technique for use with autochthonous colorectal cancer models. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 1572. doi:10.1158/1538-7445.AM2011-1572