We will develop critically-needed, non-invasive magnetic imaging agents for prostate cancer detection and staging, using a novel imaging approach that combines Magnetic Resonance Imaging (MRI) and Superconducting Quantum Interference Device (SQUID) imaging. Developing new methods for prostate cancer detection is important because it is one of the most common American-male cancers, and current detection methods result in inaccurate staging in as many as 40% of patients undergoing prostate resection. No imaging method currently exists which is specific for detecting and staging extracapsular or metastatic prostate cancer.
We aim to address this problem by developing sensitive detection methods based on magnetic imaging agents that specifically target and bind to cancer cells. These agents will consist of specific cell surface recognition ligands attached to superparamagnetic iron oxide nanoparticles (SPIONs), which can be detected by both MRI and SQUID imaging. The cell surface markers these agents will target include Prostate Specific Membrane Antigen (PSMA), Prostate Stem Cell Antigen (PSCA), the Neurotensin Receptor (NTR), and an integrin intimately involved in angiogenesis (alpha-v-beta-3). To determine which agent performs the best for the specific detection of prostate cancer, we will develop in vitro and in vivo biological models, using human prostate cancer cell lines. Expression levels for these markers will be evaluated by RT-PCR and flow cytometry in a series of human prostate cancer cell lines (LNCaP, DU-145, PC-3, and C4-2, and lines developed in house from prostatectomy specimens). The binding of the imaging agents to these cells will be measured in vitro by MRI and SQUID to select the agents or combination of agents that will provide the best MRI contrast and the highest magnetic field for SQUID detection. The same cell lines will then be used to induce primary and metastatic prostate tumors in nude mice, and MRI and SQUID detection will be used to determine the sensitivity and specificity of these intravenous agents for locating and identifying disease in vivo. The proposed work will provide the thorough understanding needed for our next goal: clinical trials of these agents for the detection and staging of primary and metastatic prostate cancer in humans by MRI and SQUID imaging. Lay terms:
We aim to develop a method to image prostate tumors and determine whether they are benign or cancerous using MRI. The proposed method would be more accurate and less invasive than needle biopsy.
|Sillerud, Laurel O (2018) Quantitative [Fe]MRI determination of the dynamics of PSMA-targeted SPIONs discriminates among prostate tumor xenografts based on their PSMA expression. J Magn Reson Imaging 48:469-481
|Sillerud, Laurel O (2016) Quantitative [Fe]MRI of PSMA-targeted SPIONs specifically discriminates among prostate tumor cell types based on their PSMA expression levels. Int J Nanomedicine 11:357-71
|Neuwelt, Alexander; Sidhu, Navneet; Hu, Chien-An A et al. (2015) Iron-based superparamagnetic nanoparticle contrast agents for MRI of infection and inflammation. AJR Am J Roentgenol 204:W302-13
|Solberg, Nathan O; Chamberlin, Ryan; Vigil, Jenette R et al. (2014) Optical and SPION-enhanced MR imaging shows that trans-stilbene inhibitors of NF-?B concomitantly lower Alzheimer's disease plaque formation and microglial activation in A?PP/PS-1 transgenic mouse brain. J Alzheimers Dis 40:191-212
|Sillerud, Laurel O; Solberg, Nathan O; Chamberlain, Ryan et al. (2013) SPION-enhanced magnetic resonance imaging of Alzheimer's disease plaques in A?PP/PS-1 transgenic mouse brain. J Alzheimers Dis 34:349-65
|Taylor, Robert M; Huber, Dale L; Monson, Todd C et al. (2012) Structural and Magnetic Characterization of Superparamagnetic Iron Platinum Nanoparticle Contrast Agents for Magnetic Resonance Imaging. J Vac Sci Technol B Nanotechnol Microelectron 30:2C101-2C1016
|Taylor, Robert M; Sillerud, Laurel O (2012) Paclitaxel-loaded iron platinum stealth immunomicelles are potent MRI imaging agents that prevent prostate cancer growth in a PSMA-dependent manner. Int J Nanomedicine 7:4341-52
|Zhao, Chenguang; Bolan, Patrick J; Royce, Melanie et al. (2012) Quantitative mapping of total choline in healthy human breast using proton echo planar spectroscopic imaging (PEPSI) at 3 Tesla. J Magn Reson Imaging 36:1113-23
|Taylor, Robert M; Severns, Virginia; Brown, David C et al. (2012) Prostate cancer targeting motifs: expression of ?? ?3, neurotensin receptor 1, prostate specific membrane antigen, and prostate stem cell antigen in human prostate cancer cell lines and xenografts. Prostate 72:523-32
|Kaini, Ramesh R; Sillerud, Laurel O; Zhaorigetu, Siqin et al. (2012) Autophagy regulates lipolysis and cell survival through lipid droplet degradation in androgen-sensitive prostate cancer cells. Prostate 72:1412-22
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