In cancer patients, determination of whether a malignancy has spread is the single most important factorused to develop a therapeutic plan and to predict prognosis. In most cases, cancer cells initially spread throughregional lymph nodes. Therefore, clinical evaluation for the presence of regional lymph node metastases is ofparamount importance. Unfortunately, there are no real-time, non-invasive clinical methods that can reliablydetect and diagnose micrometastases in lymph nodes. Therefore, there is an urgent clinical need for animaging technique that is widely available, is non-invasive and simple to perform, is safe, and can reliablydetect and adequately diagnose lymph node micrometastases in real time. The overall goal of our research program is to develop an advanced, in-vivo, noninvasive, molecularspecific imaging technology, i.e., integrated ultrasound and photoacoustic imaging combined with targetedplasmonic nanosensors, capable of immediate and accurate assessment of sentinel lymph nodemicrometastases in real time. The underlying hypothesis of this project is that photoacoustic imaging integratedwith widely used clinical ultrasound imaging is possible and both ultrasound and photoacoustic imaging can beperformed in real time, yielding an immediate diagnosis and allowing early implementation of treatment. A wide range of scientific and engineering, biomedical and clinical problems must be addressed to fullyexplore the capabilities of molecular specific ultrasound and photoacoustic lymphatic (MS-USPAL) imaging indetection and characterization of sentinel lymph node micrometastases. The current application is focused onimportant aspects of clinical translation of MS-USPAL imaging. We will develop and validate clinicallytranslatable plasmonic nanosensors for MS-USPAL. We will use ultra-small gold nanoparticles to targetepidermal growth factor receptor (EGFR), which is overexpressed in squamous carcinoma and in many otherepithelial neoplasms. For highly sensitive detection of cancer cells, we will explore EGF receptor mediatedendocytosis and the effect of plasmon resonance coupling between closely spaced molecular specificnanoparticles. The ultra-small size of nanoparticles will be highly favorable for rapid clearance from the bodywhich will allow safe transition into clinical practice. Additionally, 5 nm ligand capped gold nanoparticles willgreatly reduce nonspecific interactions and reduce the uptake of nanoparticles by immune cells such asmacrophages present due to lymph node inflammation, thus diminishing false positive results. Furthermore, wewill design and construct a prototype of the clinical MS-USPAL imaging system capable of imaging 5 nmnanoparticles in-vivo.
In cancer patients; the determination of the spread of malignancy is the single most important factor to developa therapeutic plan and predict prognosis. In most cases; cancer cells initially spread through regional lymphnodes. Thus; a technology such as molecular specific ultrasound and photoacoustic lymphatic imaging;capable of in-vivo; noninvasive and accurate assessment of regional metastases in real time; can simplify andimprove management of patients with epithelial malignancies; significantly improve public health; and reducemedical costs.
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