Real-Time Metabolic Imaging to Interrogate Early Detection and Prevention of Pancreatic Cancer
Abstract
Pancreatic ductal adenocarcinoma (PDAC) is one of the most aggressive malignancies with a dismal prognosis. Most patients present with unresectable disease and therapies are limited. It is therefore crucial to develop novel strategies for early detection and prevention. Since pancreatic premalignant lesions preceding cancer development cannot be detected by conventional imaging modalities (magnetic resonance imaging, MRI, or computed tomography, CT), PDAC preventive strategies must be developed in parallel with novel biomarkers to monitor efficacy. We propose to use hyperpolarized 13C pyruvate-based metabolic MRI for early detection of pancreatic premalignant lesions, to follow their progression in the context of preventive agents that could be easily translated into patients. Hyperpolarized MRI offers unprecedented insights into cellular metabolism in real time by enhancing the signal of conventional MRI by greater than 10,000-fold. This methodology measures metabolic changes and has proven highly sensitive for detecting pancreatic premalignant lesions to monitor immunopreventive efficacy of antibiotics. PDAC development is associated with an immunosuppressive microenvironment. Recently, studies have shown that gut bacteria associated with human and mouse PDAC is distinctive. Furthermore, PDAC-associated gut bacteria induces tumor immunosuppression and its ablation reverses it. We plan to repurpose antibiotics for PDAC prevention, including determination of best regimen and dose, and to study the mechanisms of immunomodulation in depth. Like immunotherapies, in which antitumoral responses are usually delayed, immunopreventive interventions cannot be effectively tracked by measuring tumor incidence/size at one time point. Instead, highly sensitive methods that can assess premalignant lesions and tumor incidence in live animals at real time are needed. In this translational research proposal, we plan to establish the utility of this hyperpolarized metabolic imaging to track preventive agents in murine models of premalignant neoplasia (Aim I). We will then validate the detection of early-stage PDAC in patients recently diagnosed and further explore the detection of premalignant lesions in high-risk individuals with the ultimate goal of facilitating early diagnosis and prevention of PDAC (Aim II). The research proposal will address the following two FY22 PCARP Focus Areas of (1) Early detection research for pancreatic cancer, and (2) Understanding precursors, origins, and early progression of pancreatic cancer, and will address the above hypothesis. This is a collaborative translational research proposal between the laboratories of Pratip Bhattacharya, Ph.D. (Principal Investigator, PI) in the Department of Cancer Systems Imaging, MD Anderson Cancer Center (MDACC) with Florencia McAllister, M.D. (Partnering PI) in the Department of Clinical Cancer Prevention, MDACC. Establishing the utility of this technique to track preventive agents in murine models of premalignant neoplasia as well as the clinical use on patients with high-risk lesions would be a fundamental step in moving the findings into interventional trials on patients at high risk.
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Jan 04, 2024
- Source ID
- HT94252310664
Entities
People
- Pratip Bhattacharya
Organizations
- The University of Texas MD Anderson Cancer Center
- United States Army