Molecularly Targeted Radionuclide Therapy via the Integrin Alphavbeta6
Abstract
This proposal addresses the Fiscal Year 2021 LCRP Area of Emphasis, Identify innovative strategies for the treatment of lung cancer and the congressionally mandated Metastatic Cancer Task Force Recommendation B, Diagnostics 1) Invest in novel diagnostic imaging tracers and techniques that are more sensitive and specific for the detection of early metastatic disease states and, ultimately, 2) Streamline and facilitate biomarker development for the diagnosis and monitoring of metastatic disease. We propose to evaluate a novel approach to detect and treat lung cancer that has spread to other parts of the body such as the brain, bone, and liver. The goal of this study is to improve the visualization of lung cancer and provide more effective and less toxic treatments by only targeting the cancer cells. We found that cancer cells express a protein on their surface called alphavbeta6. We have developed two molecules, 68GaGa DOTA-5G and 177LuLu DOTA-ABM-5G, that can attach to alphavbeta6. The 68GaGa DOTA-5G is injected into the bloodstream and finds the cancer cells by looking for the alphavbeta6 protein. The 68GaGa DOTA-5G is taken into the cell and can be seen using a PET scanner because of the 68Ga. The 177LuLu DOTA-ABM-5G is injected into the bloodstream and also finds the cancer cells, but when it is internalized, it kills the cancer cells because of the 177Lu. We term this combination theranostics, i.e., the combination of a diagnostic (68GaGa DOTA-5G ) and a therapeutic (177LuLu DOTA-ABM-5G). The theranostic pair 68GaGa DOTA-5G and 177LuLu DOTA-ABM- 5G was developed our team. One of the challenges in lung cancer treatment is that when the lung cancer spreads to other parts of the body, called metastasis, it becomes very difficult to treat and patients have very limited options. Therefore, we are focusing our trial on metastatic lung cancer. Any patient with metastatic lung cancer whose cancer has already progressed on standard therapy will be eligible to enroll in the clinical trial proposed. Each patient will be injected with the 68GaGa DOTA-5G. If parts of the brain, bone, or liver can be seen on the PET scan, that means that the 68GaGa DOTA-5G detected metastatic tumors, and the patient will then be given a single injection of the 177LuLu DOTA-ABM-5G treatment. Approximately 1 month later, the patient will have another 68GaGa DOTA-5G scan as well as their regular standard of care scan to see whether the tumors have shrunk. Blood samples will also be taken to make sure the therapy is not causing toxicity to the kidneys or bone marrow. Our hypotheses are that the 68GaGa DOTA-5G will be more sensitive and specific for the detection of early metastatic disease states and ultimately be used to diagnose and monitor metastatic disease; that the 68GaGa DOTA-5G and 177LuLu DOTA-ABM-5G pair will eliminate the problems of overdiagnosis and over treatment; and that 177LuLu DOTA-ABM-5G will be more effective and less toxic, as well as improve survival. As with all therapeutic interventions, there can be risks. Both 68GaGa DOTA-5G and 177LuLu DOTA-ABM-5G are radioactive molecules, so there is a potential risk; however, it is noted that they have been tested in mice at 100 times the human dose without any toxic effects, and both molecules have been injected into humans without any toxic effects. It is noteworthy that this approach does not require patients to fast and is not impacted by diabetes or inflammatory conditions. This new scan and treatment could therefore help many lung cancer patients who have difficulty due to the fasting requirements, diabetes, or inflammatory conditions. It may also eliminate the need to perform a different type of imaging, magnetic resonance imaging (MRI), which is typically used to look for cancer spread to the brain, a scan type that cannot be performed in many patients with pacemakers or metal implants in their bodies. Many Veteran
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Dec 28, 2022
- Source ID
- W81XWH2210595
Entities
People
- Julie Sutcliffe
Organizations
- United States Army
- University of California, Davis