Browsing by Author "McCowan, Caitlin"

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    Dynamic Nuclear Polarization of Silicon for Targeted Molecular Imaging
    (2019-04-17) McCowan, Caitlin; Kemere, Caleb; Bhattacharya, Pratip K.
    Colorectal cancer is the second highest cause of cancer-related deaths and is the third most commonly diagnosed cancer in America. Although there are currently available screening methods such as colonoscopy, many patients remain undiagnosed until the disease has spread and thus likely advanced beyond hope of curative treatment. Also, colonoscopy carries the risk of intestinal perforation and is less apt to identify small or flat lesions. Patients diagnosed after metastasis make up 21% of all colorectal cancer cases, with a 5-year survival rate of only 13.5%. This presents an opportunity to improve screening methods with higher accuracy and safer implementation, namely through magnetic resonance imaging (MRI) of hyperpolarized silicon particles functionalized to specifically target colorectal cancer. MRI is a commonly used imaging modality that does not require ionizing radiation. Nevertheless, sensitivity and specificity are considered to be the major drawbacks regarding MRI. One method to improve the sensitivity is through hyperpolarization, a technique used to increase signal measured with MRI by at least 10,000-fold. Silicon is a promising candidate for in vivo medical applications due to its biocompatibility. Additionally, silicon is compatible with hyperpolarization due to its MR active isotope 29Si making up 4.7% of naturally occurring silicon. I have investigated the ability to functionalize silicon particles for targeted molecular imaging of colorectal cancer in vivo through hyperpolarized MRI. Furthermore, I have explored the feasibility of utilizing hyaluronic acid-based hydrogels to improve particle targeting ability.
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    Targeted Diagnostic Imaging and Image Post-processing of Colorectal Cancer using Hyperpolarized MRI
    (2022-04-22) McCowan, Caitlin; Kemere, Caleb; Farach-Carson, Mary C; Bhattacharya, Pratip
    Colorectal cancer (CRC) is the third leading cause of cancer related deaths. While there are current methods for screening, such as colonoscopy, a number of patients remain undiagnosed until metastasis has occurred, resulting in limited treatment with unfavorable prognosis. Colonoscopy is the current standard of care, but it carries the risk of intestinal perforation and has difficulty detecting small, flat lesions. Patients diagnosed with late-stage cancer have a 5-year survival rate of 14.7%, accounting for approximately 22% of colorectal cancer patients. As early detection is key for favorable patient outcome, an improved screening method is paramount for patients unable to undergo invasive procedures. A less invasive, more quantitative method of diagnosis can be achieved using hyperpolarized magnetic resonance imaging (MRI) with a biomarker targeted imaging agent. MRI is an ideal candidate as it does not utilize ionizing radiation and offers deep tissue imaging. However, low sensitivity and low specificity have hindered its application. Hyperpolarization is a technique that can increase the sensitivity of MRI by over 10,000-fold, through dynamic nuclear polarization. Hyperpolarized MRI is compatible with several nuclear isotopes, including biocompatible elements like silicon and carbon. Additionally, by targeting mucin 1 (MUC1), a transmembrane protein overly expressed by CRC cells on their surfaces, with an imaging agent, increased specificity can be achieved. Here I describe our investigation using two new MRI-based methods to image CRC. In the first, targeted ²⁹Si microparticles were used for in vivo diagnostic imaging of CRC in a humanized MUC1-expressing mouse model. Additionally, I describe a post-processing algorithm I developed that reduces false signal, background noise, and artifacts in hyperpolarized MR images from these mice, and allows for cross-study comparison. In the second method, I developed a MUC1-targeted urease imaging construct that can be detected with hyperpolarized ¹³C-based MRI through a catabolic reaction that converts ¹³C-urea to carbon dioxide and ammonia. The targeting agent uses protein L to bind the targeting antibody and thus presents the opportunity to be used to detect a wide range of cancer-associated targets for which protein L binding antibodies are available. Together, these studies advance the field by providing new methods for non-invasive targeted imaging of CRC and potentially other cancer types.