Silver Telluride Nanoparticle Dual-Energy Mammography Contrast Agents For Breast Cancer Screening

PROJECT SUMMARY Breast cancer is the most common type of cancer for women. In addition, it leads to the second highest number of cancer deaths in women. Breast cancer screening programs using mammography and related methods reduce deaths from this disease due to early detection and are cost-effective. However, the effectiveness of mammography in women with dense breasts (which amount to about 10% of women) is poor. Furthermore, this population are independently at a higher risk of breast cancer. As a consequence, women with dense breasts are recommended to receive supplemental screening via other imaging methods. Dual-energy mammography (also known as contrast-enhanced mammography) is a supplemental screening technique that has high sensitivity and high specificity for breast cancer detection in women with dense breasts. Other imaging methods can be used for breast cancer supplemental screening, such as contrast- enhanced MRI, however, it faces challenges with reimbursement, issues of access and a high false positive rate. Dual-energy mammography is currently done with iodine-based contrast agents that are not well designed for this purpose, such as a very narrow imaging window, relatively low tumor to background ratio and allergic reactions. Novel contrast agents that addressed these issues would be highly appealing. We have recently developed silver telluride nanoparticle contrast agents for breast cancer screening via dual- energy mammography. These nanoparticles generate strong contrast for dual-energy mammography, provide a sustained imaging window, are highly stable and biocompatible and have best-in-class renal clearance. In order to advance these agents towards clinical translation, we will undertake several steps. We will adapt their synthesis so that it can be done with microfluidic chips, which allows rapid prototyping, results in homogeneous products and scale-up of the synthesis. We will characterize the nanoparticles formed from microfluidic chip scale-up and test them in a model of breast cancer. We will transfer the technology to a CRO for GMP manufacturing. With the resulting material, we will perform extensive excretion and safety studies in two species. In addition, we will perform virtual clinical trials to inform the design of clinical trials. Moreover, we will leverage the University of Pennsylvania's rich translational environment to assist in conducting a pre-IND meeting and assembling an IND application. The result of these steps will be a lead formulation ready to enter clinical trials, to enable improved detection of breast cancer and therefore lower mortality from this disease.