Novel Agent for Lymph Node Imaging and Targeted Gene Therapy
Creators: name: University Of California Office Of The President
Publisher: name: University of California Office of the President
publisherIdentifier: https://ror.org/00dmfq477
publisherIdentifierScheme: ROR
Year: 2024

description: The primary purpose of this study is to develop a contrast agent that improves detection of cancerous lymph nodes in women with breast cancer. An additional goal is to determine if the same agent can simultaneously be used to transport genetic material to cancer cells as an innovative method of cancer therapy. Depending on the size of the primary lesion at the time of the initial cancer staging (that is, the determination of the size, nature, and extent of the tumor), up to 65% of women with breast cancer have a cancer that has spread (metastasized) to the lymph nodes in the nearby area of the original cancer. Physical examination and diagnostic imaging procedures (such as X rays) are currently unreliable for determining whether or not the cancer has metastasized to the lymph nodes, and therefore surgical removal of regional lymph nodes is often required for accurate cancer staging. For those patients with cancerous lymph nodes, systemic chemotherapy, radiation therapy and/or surgery is currently necessary for control of regional disease. Although not yet routinely used, many recent studies have shown that incorporating pieces of DNA into cancer cells (gene transfection) can halt tumor growth and sometimes result in shrinkage of the tumor. Developing strategies to improve the efficiency of gene transfection could result in revolutionary changes in the way cancer is treated.
 
 
 
 
 
 
 
 Magnetic resonance imaging (MRI) is one of a number of diagnostic imaging tests currently used to evaluate lymph nodes for cancer staging. However, because lymph nodes appear similar to surrounding tissues on MR images, lymph node detection can be difficult and telling the difference between normal and cancerous nodes is often impossible. Therefore, the development of an easily administered "contrast" agent—a substance that increases the visibility of node tissue—could significantly improve lymph node detection and cancer staging accuracy.
 
 
 
 
 
 
 
 We intend to develop a new and novel contrast agent by combining a currently used MR contrast agent called Gd-DTPA with microscopic particles known as liposomes. When injected under the skin, this new contrast agent should accumulate in the small lymphatic vessels and be carried to regional lymph nodes. In the targeted node, the agent will collect and concentrate, producing a defined area of contrast enhancement. MR imaging studies will then be performed to determine the extent of enhancement of the lymph node image. Imaging properties of the agent will be evaluated both with and without genetic material (DNA) incorporated into the liposome core. We will then determine the extent of DNA uptake and expression in cells within targeted lymph nodes. Successful transport and incorporation of DNA into lymph node cells using Gd-bound liposomes would demonstrate the potential of this material to serve both as a therapeutic and as a diagnostic imaging agent. 
 
 
 
 
 
 
 
 Development of an easily administered contrast medium that enhances regional lymph node appearance on MR images could lead to earlier detection of breast cancer metastasis and more accurate cancer staging. This could also have a significant clinical impact in reducing the need for diagnostic surgical lymph node removal and its attendant complications. Directed gene therapy targeted to regional lymph nodes could also provide an ancillary or alternative approach to current regional breast cancer treatment strategies.