AlphaVBeta6-Binding Peptide Positron Emission Tomography for Staging, Response Assessment, and Patient Selection in Metastatic Non-Small Cell Lung Cancer
Abstract
This proposal addresses the FY19 LCRP Areas of Emphasis “Develop or optimize predictive markers to assist with therapeutic decision-making” and “identify innovative strategies for the treatment of lung cancer.” We are proposing a novel imaging approach to detect lung cancer. Lung cancer is the leading cause of cancer death in both women and men in the United States, with 5-year survival less than 20%, and remains a critical area of unmet need. The current standard-of-care imaging approach to determine the stage (extent) of lung cancer is [18F]-fluorodeoxy glucose positron emission tomography (PET), an imaging approach that relies on the uptake of glucose by tumors. This current imaging approach has several notable drawbacks, including the requirement that patients fast prior to imaging, difficulty in obtaining high-quality images in patients with poorly controlled diabetes, and false positives due to inflammation from causes such as chronic lung disease. This type of scan is also not effective in assessing for cancer spread to the brain, as the normal brain also has high glucose uptake. Our novel approach involves the injection of a radioactive peptide that binds specifically to a molecule on the cancer cells, the alphavbeta6 integrin. This radioactive peptide, [18F]-alphavbeta6-binding peptide (BP), has already been tested in patients with solid tumors, including lung cancer. We observed promising results, obtaining high- resolution images showing metastases to the lung, bones, adrenal, and brain; this radioactive peptide was well tolerated by all patients and therefore there is no additional risk associated with this scan. We will perform a prospective pilot clinical trial over 3 years to test this imaging approach, initially in 20 lung cancer patients with brain metastases. Each patient will have a baseline [18F]-alphavbeta6-BP PET/CT scan and a scan 2-3 months after their cancer treatment. The goals of the research are to confirm that this type of imaging will identify patients whose tumors pathologically express alphavbeta6 integrin to determine whether this scan reliably detects brain metastases, to determine whether this scan identifies the same sites of disease as conventional positron emission tomography, and to determine whether this type of scan can be used to assess response to new treatments. We will also assess tumor samples to see how many overexpress the alphavbeta6 integrin and compare the data to clinical outcomes. This will enable us to evaluate whether the alphavbeta6 integrin predicts survival and whether expression is also seen in tumors from elsewhere in the body in the same patient and will help better define which patients may benefit from this novel imaging approach and from subsequent studies testing new drugs that target the alphavbeta6 integrin. It is noteworthy that this imaging technique does not depend on glucose uptake, and hence does not require patients to fast and is not impacted by diabetes or inflammatory conditions. This new scan could therefore help many lung cancer patients who have difficulty with scans 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 that is typically used to assess 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 Veterans with lung cancer would benefit from our new imaging technique, as diabetes and inflammatory conditions like chronic obstructive pulmonary disease are common in military Veterans. It is anticipated that, during the 3-year course of study, we will develop [18F]-alphavbeta6-BP PET/CT as a safe, sensitive, specific imaging approach in lung cancer patients and use this type of scan to identify patients who will benefit from novel therapies that target alphavbeta6 integrin, such as those currently under development in our
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Mar 10, 2021
- Source ID
- W81XWH2010287
Entities
People
- Julie Sutcliffe
Organizations
- United States Army
- University of California, Davis