In vivo molecular ultrasound assessment of glioblastoma neovasculature with endoglin-targeted microbubbles

Abstract

Objectives. Glioblastoma, as one of the most malignant cancer in the world, usually shows substantially increased angiogenesis. Endoglin (CD105), which is an alternative proangiogenic growth factor, has been remarkably upregulated on the proliferating glioblastoma neovasculature. However, little is known on the noninvasive assessment of the expression levels of CD105 during glioblastoma progression. Herein, we investigated the potential of the molecular ultrasound imaging for the noninvasive assessment of the expression levels of the biomarker CD105 during the glioblastoma progression. Materials and Methods. The CD105-targeted perfluorocarbon-containing lipid-shelled microbubbles (MBs) were prepared. A parallel flow chamber was employed, in which the CD105-targeted and non-targeted MBs were tested across the CD105 +/- expression cell lines. In vivo molecular US imaging was conducted based on a subcutaneous xenograft tumor model (n = 9). Finally, the statistical analysis was conducted to quantitatively correlate the attachment numbers of MBs in the parallel flow chamber test with the CD105 expression levels of the cells in the flow cytometry test and the in vivo molecular ultrasound signals with the ex vivo expression levels of CD105 in the immunohistochemical test. Results and Discussion. The attachment numbers of the CD105-targeted MBs significantly correlated with the CD105 expression levels of the cells in the parallel flow chamber test. There was a good correlation between the in vivo molecular ultrasound signals with the CD105-targeted MBs and the ex vivo expression levels of CD105 in the immunohistochemical test. The results indicate that the molecular US imaging is much potential to assess the progression of the glioblastoma neovasculature noninvasively.