In cancer patients, determination of whether a malignancy has spread is the single most important factor used to develop a therapeutic plan and to predict prognosis. In most cases, cancer cells initially spread through regional lymph nodes. Therefore, clinical evaluation for the presence of regional lymph node metastases is of paramount importance. Unfortunately, there are no real-time, non-invasive clinical methods that can reliably detect and diagnose micrometastases in lymph nodes. Therefore, there is an urgent clinical need for an imaging technique that is widely available, is non-invasive and simple to perform, is safe, and can reliably detect and adequately diagnose lymph node micrometastases in real time. The overall goal of our research program is to develop an advanced, in-vivo, noninvasive, molecular specific imaging technology, i.e., integrated ultrasound and photoacoustic imaging combined with targeted plasmonic nanosensors, capable of immediate and accurate assessment of sentinel lymph node micrometastases in real time. The underlying hypothesis of this project is that photoacoustic imaging integrated with widely used clinical ultrasound imaging is possible and both ultrasound and photoacoustic imaging can be performed 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 fully explore the capabilities of molecular specific ultrasound and photoacoustic lymphatic (MS-USPAL) imaging in detection and characterization of sentinel lymph node micrometastases. The current application is focused on important aspects of clinical translation of MS-USPAL imaging. We will develop and validate clinically translatable plasmonic nanosensors for MS-USPAL. We will use ultra-small gold nanoparticles to target epidermal growth factor receptor (EGFR), which is overexpressed in squamous carcinoma and in many other epithelial neoplasms. For highly sensitive detection of cancer cells, we will explore EGF receptor mediated endocytosis and the effect of plasmon resonance coupling between closely spaced molecular specific nanoparticles. The ultra-small size of nanoparticles will be highly favorable for rapid clearance from the body which will allow safe transition into clinical practice Additionally, 5 nm ligand capped gold nanoparticles will greatly reduce nonspecific interactions and reduce the uptake of nanoparticles by immune cells such as macrophages present due to lymph node inflammation, thus diminishing false positive results. Furthermore, we will design and construct a prototype of the clinical MS-USPAL imaging system capable of imaging 5 nm nanoparticles in-vivo.
In cancer patients, the determination of the spread of malignancy is the single most important factor to develop a therapeutic plan and predict prognosis. In most cases, cancer cells initially spread through regional lymph nodes. 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 and improve management of patients with epithelial malignancies, significantly improve public health, and reduce medical costs.
|Hannah, Alexander S; Luke, Geoffrey P; Emelianov, Stanislav Y (2016) Blinking Phase-Change Nanocapsules Enable Background-Free Ultrasound Imaging. Theranostics 6:1866-76|
|Luke, Geoffrey P; Hannah, Alexander S; Emelianov, Stanislav Y (2016) Super-Resolution Ultrasound Imaging in Vivo with Transient Laser-Activated Nanodroplets. Nano Lett 16:2556-9|
|Mallidi, Srivalleesha; Kim, Seungsoo; Karpiouk, Andrei et al. (2015) Visualization of molecular composition and functionality of cancer cells using nanoparticle-augmented ultrasound-guided photoacoustics. Photoacoustics 3:26-34|
|Qu, M; Mehrmohammadi, M; Emelianov, S Y (2015) Sensing the delivery and endocytosis of nanoparticles using magneto-photo-acoustic imaging. Photoacoustics 3:107-13|
|Luke, Geoffrey P; Emelianov, Stanislav Y (2015) Label-free Detection of Lymph Node Metastases with US-guided Functional Photoacoustic Imaging. Radiology 277:435-42|
|Wu, Chun-Hsien; Sokolov, Konstantin (2014) Synthesis of immunotargeted magneto-plasmonic nanoclusters. J Vis Exp :|
|Luke, Geoffrey P; Myers, Jeffrey N; Emelianov, Stanislav Y et al. (2014) Sentinel lymph node biopsy revisited: ultrasound-guided photoacoustic detection of micrometastases using molecularly targeted plasmonic nanosensors. Cancer Res 74:5397-408|
|Kim, Seungsoo; Chen, Yun-Sheng; Luke, Geoffrey P et al. (2014) In-vivo ultrasound and photoacoustic image- guided photothermal cancer therapy using silica-coated gold nanorods. IEEE Trans Ultrason Ferroelectr Freq Control 61:891-7|
|Qu, Min; Mehrmohammadi, Mohammad; Truby, Ryan et al. (2014) Contrast-enhanced magneto-photo-acoustic imaging in vivo using dual-contrast nanoparticles. Photoacoustics 2:55-62|
|Luke, Geoffrey P; Emelianov, Stanislav Y (2014) Optimization of in vivo spectroscopic photoacoustic imaging by smart optical wavelength selection. Opt Lett 39:2214-7|
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