Noninvasive Diagnostic Imaging of Polyamine Metabolism in Lung Cancer
Abstract
Among the different types of malignant tissues, lung cancer, by far, is the deadliest form since it accounts for the greatest number of cancer-related deaths in the U.S. and even worldwide. Recent statistics have shown that the average 5-year survival rate for lung cancer patients is only about 15 percent—a relatively high mortality rate that reflects on the difficulty of early diagnostics of this disease that devastates a very important organ in the body. A major reason as to why this disease is so deadly is because lung cancer patients often do not show any obvious symptoms at the early stage, and this disease often takes decades to develop. However, by the time the symptoms become evident, this disease could already be metastatic. Therefore, lung cancer is often diagnosed when it has already progressed significantly and when standard therapeutic intervention is already too late to implement. This study seeks to capitalize on this aberrant polyamine biochemical pathway in non-small cell lung cancer (NSCLC) and turn it into a diagnostic advantage for the early noninvasive detection and metabolically accurate assessment of lung cancer with molecular precision. So far, urine and plasma tests of elevated polyamine levels are used in the diagnostic arsenal for cancer screening. While urine and plasma polyamine level tests are quite useful for early cancer screening and will continue to be so, these assay-based techniques lack the biochemical information onsite in actual NSCLC tumors. So far, there is currently no real-time, in vivo imaging technology that can track and image not only the uptake of ornithine, but also its expected high production of polyamines production across the lung tumors. The FY21 LCRP Areas of Emphasis of this project are: (1) to identify innovative strategies for the screening and early detection of lung cancer and (2) to develop or optimize prognostic or predictive markers to assist with therapeutic decision-making. In this project, the biocompatible, non-radioactive 13C-labeled polyamine tracer ornithine (a biochemical that is endogenous or present in human cells) will be used as a diagnostic spy for early screening and accurate detection of lung cancer by capitalizing on the addiction of lung tumors on this biochemical. Aided by hyperpolarization technology, which enhances the MRI signals by >10,000-fold, this study will track the expected high uptake of polyamine raw material in lung tumors and the high production of polyamine biochemical products, which are indicative of tissue malignancy. By far, this is the only potential non-invasive imaging technique that has the capability and specificity to map out not only the uptake of ornithine in lung cancer, but also its ensuing metabolic products (e.g., putrescine and possibly other polyamines)—diagnostic information that cannot be acquired in other imaging modalities such as PET and CT scans. This implies that a clear-cut diagnostic tool with high specificity and superb sensitivity could potentially be developed using imaging agents that are nonradioactive and biocompatible since they are endogenous or present in our cells. In other words, this proposed research study could potentially provide a new non-invasive and high-resolution imaging tool for lung cancer diagnostics with molecular precision for our military and the public in general.
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Dec 28, 2022
- Source ID
- W81XWH2210003
Entities
People
- Lloyd Lumata
Organizations
- United States Army
- University of Texas at Dallas