|Title:||In vivo molecular imaging and assessment of tumor microenvironment by ultrasound and photoacoustics|
|Advisors:||Sun, Lei (BME)|
|Subject:||Cancer -- Molecular aspects|
Tumors -- Molecular aspects
Molecular probes -- Diagnostic use
Cancer -- Diagnosis
Hong Kong Polytechnic University -- Dissertations
|Department:||Department of Biomedical Engineering|
|Pages:||vi, 127 pages : color illustrations|
|Abstract:||Tumor angiogenesis and tumor microenvironment are two critical hallmarks for tumorigenesis. Tumor angiogenesis, the production of new vasculature from existing mature vessels, contributes a lot to tumorigenesis. Angiogenesis, however, is not a single step activity, but regulated by quite a number of growth factors, either as promoter or inhibitor. Endoglin (CD105), as one pro-angiogenic biomarker, has been found to be highly expressed on proliferating neo-vasculatures at the early stage of angiogenesis. However, little is known on the in vivo expression levels of endoglin (CD105) during the progression of glioblastoma. Molecular ultrasound imaging, which employs functionalized microbubbles (MBs) as contrast agent, is potentially able to assess tumor angiogenesis non-invasively and quantitatively. Owing to their micron size (1~4 μm in diameter) of microbubbles, molecular ultrasound imaging is highly suitable for imaging angiogenic molecular markers on blood vessels. In this thesis, molecular ultrasound imaging with the aid of CD105-targeted microbubbles (MBs) was utilized to quantify the endoglin expression levels of glioblastoma. The results showed that CD105-targeted molecular ultrasound imaging was able to provide non-invasive and high-resolution imaging and assessment of glioblastoma angiogenesis in real time. The understanding of protease activity requires the assessment of proteolytic activity in the tumor microenvironment rather than simply evaluation of the expression levels of proteases because the expression of any individual protease alone can not represent the proteolytic activity. It is necessary to better understand the roles and functions of a particular protease. Regarding this, we have taken protease MMP-2 as an example. Molecular photoacoustic imaging, with the aid of properly designed contrast agent, is potential to contribute to the non-invasive imaging and assessment of protease activity in vivo. This molecular imaging strategy is potential to provide not only deep penetration and high spatial resolution, but also specific patho-physiological information in molecular level in real-time. Furthermore, photoacoustic imaging (PAI) is emerging as a new powerful tool to offer unique chromophore identification information in tumor microenvironment (TME) which isunique for non-invasive imaging and assessment ofthe proteolytic activity in vivo. In this thesis, we systematically investigated the application of gold nanocage-based cleavable nanoprobe to image the proteolytic activity in vivo, by utilizing photoacoustic imaging technique. The potential of this strategy to image the distribution of the tumor protease activity was validated in vitro, in cultured cells, and in a subcutaneous xenograft tumor model in vivo. The results provided valuable evidences for further development of such novel molecular photoacoustic imaging strategy for investigation of tumor protease activity in vivo.|
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