Molecular and functional ultrasound imaging of breast tumors

Among women breast cancer is the most frequently diagnosed cancer worldwide [1]. The early detection of breast cancer can lead to decreased mortality rates, therefore accurate and sensitive imaging techniques are required. Among the typical breast imaging techniques ultrasound has proven to be more sensitive in the diagnosis of breast cancer in dense breast tissue compared to mammography [2]. Contrast enhanced ultrasound in patients with malignant breast lesions showed that the enhancement patterns and the specific parameters of contrast enhanced ultrasound, like peak enhancement or area under the time-intensity curve, may help to predict prognosis and to noninvasively detect highly aggressive breast cancers [3]. A further technique to characterize the breast cancers’ aggressiveness may be molecular ultrasound imaging. In this technique ultrasound contrast agents, i.e. microbubbles, targeting endothelial angiogenic markers are used. Angiogenesis is the formation of blood vessels from pre-existing ones [4] and angiogenic markers are overexpressed on the endothelium of various tumors [5]. Markers that have so far been mostly targeted in molecular ultrasound imaging include the vascular endothelial growth factor receptor type 2 (VEGFR2), alpha-v-beta-3-integrin (avb3-integrin) and endoglin [6]. In preclinical settings molecular ultrasound imaging of breast cancer models has been shown not only to be feasible but also to lead to an accurate depiction of the angiogenic marker expression within the tumors. The retention of VEGFR2-targeted microbubbles correlated well with the VEGFR2 expression in breast cancer models [7,8]. Further, RGD-labelled microbubbles targeting avb3-integrin were shown to bind in breast cancer xenografts [9]. Consecutive imaging of various markers within one imaging session was shown to be possible in a skin cancer model [10] and was also suitable for the assessment of VEGFR2, avb3-integrin and endoglin expression in small, medium and large breast tumors [11].