Quantitative Imaging of Polyfluoroalkyl Substances Based on the Reversal of Albumin Luminescence

Abstract

Per- and polyfluoroalkyl substances (PFASs) are human-made environmental contaminants of global concern due to their extreme persistence and potential adverse health effects, and elucidating their physiological impacts remains a critical challenge. In this study, we present a molecular imaging platform that enables quantitative visualization of PFAS effects in vivo and in vitro by indexing the reversal of albumin luminescence mediated by specially designed coelenterazine (CTZ) analogues as optical indicators. We synthesized a list of CTZ analogues to facilitate luminescence upon binding with specific albumins; this signal is efficiently suppressed by PFAS compounds. We found that perfluorooctanoic acid (PFOA) and perfluorooctanesulfonic acid (PFOS) dose dependently suppressed bovine serum albumin luminescence, a feature consistent across multiple mammalian albumins, including humans. Further in vivo imaging revealed rapid absorption of PFOS into the liver of living mice and a marked 41% reduction in hepatic luminescence, suggesting that acute exposure suppresses the normal liver activity. This study represents the first albumin-based molecular imaging platform for assaying the potential physiological impacts of PFASs in vivo and in vitro, offering a practical and adaptable tool for environmental monitoring and toxicological evaluation.