Department of Biomedical Engineering Final Oral Examination Quan Zhou In Vivo Molecular Targeted Photoacoustic Imaging of Cancer Cancer is a group of more than 100 diseases that develop across time and involve the
Department of Biomedical Engineering Final Oral Examination
In Vivo Molecular Targeted Photoacoustic Imaging of Cancer
Cancer is a group of more than 100 diseases that develop across time and involve the uncontrolled division of the body’s cells. It develops step-by-step, across time, as an accumulation of many molecular changes, each contributing some of the characteristics that eventually produce the malignant state. Many strategies have been developed to target these molecular changes, such as antibodies, aptamers, small molecules and lectins. Among them, affinity peptides are much smaller than antibodies, and can achieve greater extravasation from leaky tumor vasculature, enhanced tissue diffusion, and higher drug concentration in tumors. Photoacoustic imaging is an emerging optical imaging technique that is capable of providing both structural and functional optical information of tissues up to several centimeters deep with scalable ultrasound resolution. The combination of ultrasound spatial resolution and intrinsic rich optical contrast in cancer make photoacoustic imaging a promising early detection tool in diagnostic medicine. Conventional photoacoustic imaging mainly relies on intrinsic non-specific contrast such as hemoglobin and pigmentation to visualize diseases. If exogenous contrast agents can be modified with cancer biomarker targetability, photoacoustic imaging will provide specific functional information in high contrast for cancer diagnosis and guided surgery.
This dissertation is presenting photoacoustic imaging of two cancer cell surface biomarkers, Epidermal Growth Factor Receptor (EGFR) and Glypican-3 (GPC3), important in the development of hepatocellular carcinoma (HCC). Short peptide sequences specifically targeting these biomarkers have been selected and validated in vitro and in vivo. They demonstrated high target affinities (kd<75 nM) and fast cellular binding kinetics (<10 min), which are desirable for clinical settings of early diagnosis and surgical guidance. After conjugating with organic dye and gold nanoshell, respectively, these molecular targeting probes were able to home to the HCC tumor xenograft in vivo after intravenous administration. High target-to-background ratio (2.25±0.25) was achieved in vivo after 2-3 hours and specific binding was confirmed in resected xenograft tumor tissues. In vivo cell surface binding of peptide probe to HCC xenograft in mice was observed at subcellular resolution in both horizontal (1000×1000 µm2) and vertical (1000×430 µm2) planes with hand held dual-axis confocal microscope. The targeting probe was able to distinguish HCC from non-HCC human patient biopsies (n=41) at 93% sensitivity and 88% specificity. These studies show that affinity peptide based molecular imaging is an enabling technology which will allow clinicians to perform functional imaging of patients to identify early cancer lesion or surgical resection margin with high accuracy and contrast. Date: Thursday, June 22, 2017 Time: 9:00 AM Location: 3813 Medical Science II Chair: Thomas D. Wang
(Thursday) 9:00 am - 10:00 am
3813 Medical Science II
1137 Catherine St, Ann Arbor, MI 48109