Early Detection of Prostate Cancer with New Nanoparticle-Based Ultrasound Contrast Agents Targeted to PSMA
Abstract
Prostate cancer is a deadly disease claiming the lives of nearly 30,000 men per year in the United States alone. The standard of care for patients suspected to have prostate cancer following abnormalities on digital rectal exams and/or prostate serum antigen screening is transrectal ultrasound imaging and a tissue biopsy taken from several areas within the prostate suspected to have cancer. Often, the tissue sampled by the biopsy does not represent the actual area of interest because many biopsies are done with no image guidance. Even those biopsies carried out under ultrasound guidance may not be accurate due to poor resolution and low contrast differences between the normal prostate and cancer tissue. Because of this, many men are not diagnosed with prostate cancer, or the results may not be representative of the entire tumor. For example, an area of the cancer that is more aggressive or of a higher grade may not have been biopsied at all. Such errors can lead to increased patient pain and suffering and elevated healthcare costs, since retesting and repeated biopsies are often needed in the long term. Some complex procedures such as magnetic resonance imaging (MRI)-guidance of the biopsy process have been shown to be advantageous in capturing more representative tumor biopsy samples. However, this technology is not widely available and accessible, procedures are very lengthy, and the cost is quite high. Ultrasound-guided biopsies have not been shown to be better than blind biopsies done without any image guidance at all. In this application, we propose a more effective way to address this problem with ultrasound imaging that is enhanced by a tumor-targeted contrast agent. Specifically, we will combine expertise from a biomedical engineering laboratory and a radiological research laboratory focused on different aspects of the molecular imaging research field to create a new tool - nanoparticle-sized ultrasound contrast agents that are targeted to a receptor that can be found on the surface of most prostate cancer cells. We call the nanoparticles nanobubbles (or NBs) because they are gas filled phospholipid vehicles similar in structure and stability to a soap bubble. These NBs are targeted to the prostate serum membrane antigen (PSMA) receptor with a urea-peptide attached to their surface. The peptide was developed and characterized by the Basilion team, while the NBs were developed by the Exner team. Bringing these two technologies together will create a better solution to more accurate biopsies. The detection of these agents can be done with standard ultrasound equipment, which has contrast imaging capabilities (as most do nowadays) that is widely accessible, low cost, and will not require specialized equipment. Our hypothesis is that the PSMA-targeted NBs will be able to hone and attach to prostate cancer cells and their signal will more accurately with higher resolution delineate prostate cancers. The proposed research will answer three key questions that will enable our approach to be properly characterized and optimized for the next steps: (1) Can the PSMA targeted NBs actually detect prostate cancer in a mouse model? (2) Are the contrast agent associated parameters distinct from the clinically available microbubbles? (3) Do the PSMA-NBs delineate prostate cancer more effectively than microbubbles? The work will be done in three aims. The first aim will be used to formulate and characterize the NB formulation and examine binding efficiency to cells in culture. The second aim will examine NB biodistribution in PSMA positive and PSMA negative tumors in mice. Finally, the third aim will test the prostate cancer detection using PSMA-NB using radio-pathologic correlation. While ultrasound contrast agents are not a new idea, our NBs perform fundamentally differently because they are small (100 nanometers) and can easily move outside of the blood vessels and into the tumor tissue itself through "le
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Jan 31, 2017
- Source ID
- W81XWH1610372
Entities
People
- James P Basilion
Organizations
- Case Western Reserve University
- United States Army