Characterization of a murine xenograft model for contrast agent development in breast lesion malignancy assessment

Background: the aim of the study was to develop a nude mouse xenograft model implanted with both benign and malignant xenografts as the preliminary candidate screening tool for contrast agent development in lesion malignancy indication. results: a malignant xenograft (either mcf-7 cell/matrigel™ or mda-mb 231 cell/matrigel) and a benign xenograft (culture medium/matrigel) with cleft and slit-like features of intracanaliculer fibroadenoma were implanted subcutaneously into flanks of individual nu/nu nude mouse with >90 % successful inoculation rate. both malignant and benign xenografts with volume up to 4 cm3 and (size up to 2 cm) after 5th week were characterized in vivo by sonogram (exhibiting endogenous morphological contrast features between benign and malignant xenografts),dynamic contrast enhanced multi-detector computed tomography (presenting non-targeting exogenous morphological and dynamic contrast features between benign and malignant xenografts),and then were harvested for histological and immunohistochemistry (revealing example of targeting/molecular contrast features,such as expression of cancer vascular markers of malignant xenografts). malignant xenografts appeared morphologically taller than wide (axis parallel to skin) with angular/ill-defined margin under sonogram observations,revealed more evident rim enhancement,angular margin and washout pattern in the time-density curve from dynamic contrast enhance multi-detector computed tomography images,and had more visible cancer vascular markers (cd31 and vegf) expression. with limited number of subjects (5-27 for each group of a specific imaging contrast feature),those imaging contrast features of the xenograft model had larger than 85 % sensitivity,specificity,accuracy,positive and negative prediction values in indicating xenograft malignancy except for results from color doppler detections. conclusions: the murine xenograft model might provide an earlier efficacy evaluation of new contrast agent candidate for lesion malignancy interrogation with qualitative and quantitative indication before a human study to reduce the risk and conserve the resources (time,finance and manpower). © 2016 yen et al.