Fluorescence imaging is a popular biomedical tool used in basic science and clinical practice such as disease diagnosis and surgery. The agents used in fluorescence imaging can exhibit some degree of phototoxicity (damage due to light). In recent years, there has been an increasing number of fluorescence imaging products reviewed by the U.S. Food and Drug Administration, and the issue of phototoxicity is of significant interest. The lack of established, well-validated test methodologies and scientific expertise on the topic of fluorescent agent phototoxicity risks the clearance of products with toxic potential, or conversely, excessive iteration with sponsors on testing of benign agents, leading to unnecessary delays in product marketing. Therefore, the goal of this one-year NSF/FDR Scholar in Residence project is to establish standardized methods for evaluating phototoxicity of emerging fluorescence imaging products in living cells. Through proper dissemination and incorporation of gained knowledge, the project will be able to vastly improve the likelihood that safe and effective fluorescence imaging products are translated into clinical use in a timely manner. The planned research will be seamlessly integrated with educational, mentoring, and outreach activities to advance the cross-disciplinary program in the field of biophotonics and regulatory science. The results will be disseminated broadly through journal publications, conferences, and workshops held jointly at FDA and UMD. This work will be presented at conferences on biomedical optics, molecular imaging, and photobiology. The findings will be presented to regulatory reviewers in Center for Devices and Radiological Health (CDRH) to make informed regulatory decisions.
The overall purpose of this project is to generate knowledge and testing tools as a foundation for improving regulatory evaluation of photo-cytotoxicity in emerging fluorescence imaging combination products. The project is motivated by the need for standardized safety test methods in the emerging "combination product" reviewed in the Center for Drug Evaluation and Research (CDER) and Center for Devices and Radiological Health (CDRH), and a better scientific understanding of factors influencing fluorescent agent safety. The project will systematically characterize the photosensitizing properties of established and emerging fluorophores in cell-based systems. Biologic effects will be correlated with basic photochemical and photophysical parameters to fully understand the mechanisms underlying the photosensitization. Studies are designed to achieve two research objectives: (1) quantify photo-cytotoxicity of established and emerging fluorophores using 3T3 Neural Red Update (NRU) and other testings and (2) establish standardized best practices for evaluating the phototoxicity of fluorophores. The primary outcomes of this project will be a battery of test methods – protocols for standardized assaying, data acquisition, and processing – that represent best practices for evaluating the phototoxicity of emerging fluorescence imaging agents in cells. Additionally, biologic effects will be correlated with basic photochemical and photophysical parameters to fully understand the mechanisms underlying the photosensitization.
This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.
